0000000000037994
AUTHOR
José M. Vila
EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study
Abstract Introduction and objectives Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in epithelium adhesion, is an understudied area in the MVO setting. We aimed to determine whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods We prospectively included 106 patients with a first STEMI treated with percutaneous coronary intervention, quantifying serum levels of EpCAM 24 hours postreperfusion. All patients underwent CMR imaging 1 w…
Aspirin and COX-2 Inhibitor Nimesulide Potentiate Adrenergic Contractions of Human Gastroepiploic Artery
Background The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine. Methods Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition. Results The COX-1 and COX-2 inhibitor aspirin at high concentrations (10 −6 to 10 −5 mol/L) and the COX-2 inhibitor nimesulide (10 −6 mol/L…
PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits
Abstract Background and aims Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another. Methods In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis. Results MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodi…
EpCAM y obstrucción microvascular en pacientes con un IAMCEST: estudio con resonancia magnética cardiaca
Resumen Introduccion y objetivos La obstruccion microvascular (OMV) se asocia negativamente con la estructura cardiaca y el pronostico de los pacientes tras un infarto agudo de miocardio con elevacion del segmento ST (IAMCEST). El factor epithelial cell adhesion molecule (EpCAM), implicado en la cohesion de las celulas epiteliales, esta poco estudiado en el contexto de la OMV. Por ello, el objetivo de este estudio es evaluar en una cohorte de pacientes con IAMCEST la asociacion entre la concentracion de EpCAM circulante con la extension de la OMV, determinada por resonancia magnetica cardiaca (RMC), y la funcion sistolica en fases cronicas. Metodos Se incluyo prospectivamente a 106 paciente…
Effects of sildenafil on human penile blood vessels.
Abstract Objectives. To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfunction. Methods. Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, and the isometric tension was recorded. We then studied the effects of sildenafil on precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses. Results. Sildenafil (10 −9 to 3 × 10 −6 M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprus…
Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin.
Abstract The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1–8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10−6 M). Noradrenaline induced concentration-dependent contractions with an EC50 of 1.85 × 10−6 M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, NG-nitro- l …
Arginine Vasopressin Enhances Sympathetic Constriction Through the V 1 Vasopressin Receptor in Human Saphenous Vein
Background —Arginine vasopressin (AVP) not only acts directly on blood vessels through V 1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. Methods and Results —Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3×10 −9 mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectiv…
Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation
Abstract The present study was designed to investigate the influence of endothelium-derived nitric oxide on the contractile responses of isolated human omental arteries to electrical field stimulation and noradrenaline. We measured isometric tension in artery rings obtained from portions of human omentum during the course of abdominal operations (32 patients). Electrical field stimulation induced frequency-dependent contractions which were abolished by tetrodotoxin (10−6 M) and prazosin (10−6 M), thus indicating that this effect was due to noradrenaline released from adrenergic nerves acting on α1-adrenoceptors. The increases in tension induced by electrical field stimulation were of greate…
Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction
Abstract Introduction and objectives Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models…
Neurogenic contraction and relaxation of human penile deep dorsal vein
The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. Electrical field stimulation (0.5–2 Hz) and noradrenaline (3×10−10–3×10−5M) caused frequency- and concentration-dependent contractions that…
Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI
Abstract Aims Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest. Methods Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months. mRNA expression of genes implicated in lymphocyte activation (CD25 and CD69) and regulation …
Chronic exercise impairs nitric oxide pathway in rabbit carotid and femoral arteries
KEY POINTS: Some of the beneficial effects of exercise in preventing vascular related diseases are mediated by the enhancement of endothelial function where the role of nitric oxide (NO) is well documented, although the relevance of calcium activated potassium channels is not fully understood. The impact of oxidative stress induced by training on endothelial function remains to be clarified. By evaluating different endothelial vasodilator pathways on two vascular beds in a rabbit model of chronic exercise, we found a decreased NO bioavailability and endothelial nitric oxide synthase expression in both carotid and femoral arteries. Physical training induced carotid endothelial dysfunction as…
Inhibition of nitric oxide activity by arginine analogs in human renal arteries
Abstract Background: Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study we tested the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries. Methods: Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ baths for isometric recording of tension. We then studied the effects of N G -monomethyl- l -arginine (L-NMMA), N G , N G -dimethyl- l -arginine (asymmetrical dimethylarginine [ADMA]), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated cond…
Inhibition of neuroeffector transmission in human vas deferens by sildenafil
Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP…
Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.
We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.
Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of human gastroepiploic artery and saphenous vein.
Objective: The present experiments were designed to evaluate differences in the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses of human gastroepiploic artery and saphenous vein elicited by vasopressin. Design: Laboratory investigation. Setting: University laboratory. Subjects: Rings of human gastroepiploic artery were obtained from 32 patients undergoing gastrectomy, and rings of saphenous vein were obtained from 30 patients undergoing coronary artery bypass surgery. Interventions: The rings were suspended in organ baths for isometric recording of tension. We studied the responses to vasopressin in the absence and in the presence of either the vasopressin V …
Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients.
Cardiovascular manifestations are frequent findings in patients with thyroid hormone disorders. Nitric oxide (NO) plays a key role in vascular, endothelial-mediated relaxation. NO is synthesized from L-arginine by NO synthase, an enzyme inhibited by endogenous compounds, mainly asymmetric dimethylarginine [asymmetric N(G),N(G)-dimethyl-L-arginine (ADMA)]. The aim of our work was to investigate whether plasma L-arginine and dimethylarginine concentrations and NO production are altered in hypo- and hyperthyroid patients, compared with control subjects. L-arginine, ADMA and symmetric dimethylarginine were analyzed by HPLC. NO was measured as plasma nitrite plus nitrate (NO(x)) concentration by…
Implicación de la isoforma antiangiogénica VEGF-A165b en la angiogénesis y la función sistólica tras un infarto de miocardio reperfundido
Resumen Introduccion y objetivos La angiogenesis participa en la restauracion de la microcirculacion despues de un infarto agudo de miocardio (IAM). El objetivo de este estudio es explorar el papel que juega la isoforma anti-angiogenica del factor de crecimiento endotelial vascular (VEGF)-A165b y explorar su potencial como terapia coadyuvante a la reperfusion coronaria. Metodos Se realizaron dos modelos murinos de IAM: a) ligadura permanente de la arteria coronaria (IAM no reperfundido) y b) oclusion transitoria durante 45 minutos de la arteria coronaria seguida de reperfusion (IAM reperfundido); en ambos modelos, se realizo a los animales una ecocardiografia previa a la eutanasia el dia 21…
Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary artery: role of thromboxane A(2).
Abstract To examine whether low concentrations of endothelin-1 potentiate the vasocontrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10 −10 M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET B receptor antagonist (2,6-dimethylpiperidinecarbonyl-γ-methyl-Leu- N in -[Methoxycarbonyl]- d -Trp- d -Nle) (BQ-788, 10 −6 M), but not the endothelin ET A receptor antagonist cyclo( d -Asp-Pro- d -Val-Leu- d -TRP) (BQ-123, 10 −6 M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibit…
EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Bachground. Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in endothelium adhesion, is an understudied area in the MVO setting. Purpose. We aimed to evaluate whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods.…
Influence of Endothelial Nitric Oxide on Adrenergic Contractile Responses of Human Cerebral Arteries
The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3–8 h before. EFS (1–8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10-6 M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-monomethyl L-arginine (L-NMMA 10-4 M) potentiated the contractile response to EFS in artery rings with endothelium but did not …
Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin
Purpose: The goal of this study was to determine the effects of vasopressin and the selective V 2 -receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. Methods: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V,-receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 −6 mol/L), the V 1 -V 2 receptor antagonist desGly-d(CH 2 ) 5 D-T…
Role of Ca2+-Activated K+ Channels on Adrenergic Responses of Human Saphenous Vein
Background We studied the participation of K + channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca 2+ channels on modulation of adrenergic responses by K + channels blockade. Methods Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. Results Iberiotoxin (10 −7 mol/L), an inhibitor of large conductance Ca 2+ -activated K + channels, and charybdotoxin (10 −7 mol/L), an inhibitor of both large and intermediate conductance Ca 2+ -activated K + channels, enhanced the contractions elicited by elec…
Function of Glia in Aging and the Brain Diseases.
Microglia cells during aging, neurodegeneration and neuroinflammation show different morphological and transcriptional profiles (related to axonal direction and cell adhesion). Furthermore, expressions of the receptors on the surface and actin formation compared to young are also different. This review delves into the role of glia during aging and the development of the diseases. The susceptibility of different regions of the brain to disease are linked to the overstimulation of signals related to the immune system during aging, as well as the damaging impact of these cascades on the functionality of different populations of microglia present in each region of the brain. Furthermore, a decr…
Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19
This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower mi…
Material multimedia para aumentar el rendimiento académico de los trabajos en grupo
[EN] Multimedia can be considered a useful tool for improving the learning. In this study we analyze the marks that students get in a group activity with and without the use of a multimedia material made by teachers. The scores are obtained using a rubric previously tested for this activity and the results show an increase in the final qualification for student groups who used the multimedia material. We also analyze the scores by units following the rubric and we note that scores increase 4.0 points for a maximum of 10 in the methodology unit. Moreover, we collect the opinion of our students about the multimedia material and how it helped them to better understand the work they had to do i…
Relaxation and cGMP formation in response to sildenafil and sodium nitroprusside in saphenous veins from normotensive and hypertensive patients1
Abstract Background This study was designed to measure cyclic guanosine 3′5′ monophosphate (cGMP) formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside in saphenous veins obtained from normotensive and hypertensive patients. Methods Saphenous vein rings were obtained from 13 hypertensive and nine normotensive patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. The effect of sildenafil on sodium nitroprusside-induced cGMP formation was also assessed. Results Sildenafil (10 nmol/L to 100 μmol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused c…
Ca2+-activated K+ channels mediate relaxation of forearm veins in chronic renal failure
In arteries, agonists such as acetylcholine release an endothelium-derived hyperpolarizing factor (EDHF) that is neither nitric oxide nor prostacyclin.To examine the responses to acetylcholine in segments of forearm veins from patients with chronic renal failure who either had never received dialysis or had undergone long-term dialysis, and to determine the contribution of nitric oxide and EDHF to endothelium-dependent relaxation in veins from patients with chronic renal failure.Isometric tension was recorded in rings of forearm vein from 34 non-dialysed patients, 27 dialysed patients and 14 multiorgan donors (controls).Relaxation in response to acetylcholine was reduced in veins of non-dia…
Bifidobacterium pseudocatenulatum CECT 7765 supplementation restores altered vascular function in an experimental model of obese mice
Aims. Bifidobacterium pseudocatenulatum CECT 7765 improves metabolic and immunological altered functions in high fat fed mice, however little is known about the effects of potential probiotics on vascular reactivity. The aim of the present study was to investigate the effects of a potential probiotic strain, Bifidobacterium pseudocatenulatum CECT 7765, on vascular response in obese mice. Methods. Aorta samples were obtained from mice, which were divided into three groups: a control group, receiving a standard diet; an obese group, receiving a high-fat diet; and an obese group receiving high-fat diet and a daily dose of B. pseudocatenulatum CECT 7765 by oral gavage. Aortic rings were suspend…
Contractile responses of human thyroid arteries to vasopressin
Abstract Aims In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors. Main methods Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration–response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 − 8 M), the nitric oxide synthase inhibitor N G -monomethyl- l -arginine ( L -NMMA, 10 − 4 M), or the inhibitor of prostaglandins indom…
Modulation of adrenergic responses of human vas deferens by K+ channel inhibitors.
Objectives The present study was designed to evaluate the role of K + channels in the adrenergic responses of human vas deferens as well as the intervention of dihydropyridine-sensitive Ca 2+ channels on modulation of adrenergic responses by K + channel inhibitors. Methods Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of K + channel blockers on neurogenic and norepinephrine-induced contractile responses. Results Addition of tetraethylammonium (TEA, 10 −3 M), a nonspecific K + channel blocker, or charybdotoxin (10 −7 M), a nonselective inhibitor of lar…
Influence of nitric oxide on neurogenic contraction and relaxation of the human gastroepiploic artery.
Abstract Background The objective of this study was to characterize the neurogenic contraction and relaxation of the human gastroepiploic artery and to determine whether the responses are mediated by nitric oxide (NO) from neural or endothelial origin. Methods Rings of human gastroepiploic artery were obtained from 18 patients (12 men, 6 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the contractile and relaxant responses to electrical field stimulation. Results In arteries under resting conditions, electrical field stimulation (2 to 8 Hz) caused frequency-dependent contractions that were of greater magnitude in arteries…
V2-receptor–mediated relaxation of human renal arteries in response to desmopressin
The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and …
Ischemia-reperfusion injury to coronary arteries: Comprehensive microscopic study after reperfused myocardial infarction.
Abstract Background Coronary arteries supply oxygen and nutrients to the heart. We evaluated the dynamics of microscopic damage throughout the ischemia-reperfusion process in the wall of coronary arteries following myocardial infarction (MI). Methods In a swine model of reperfused MI, animals were divided into one control and four MI groups: 90-min ischemia without reperfusion, or followed by one minute, one week or one month reperfusion. Left anterior descending (LAD; infarct-related artery) and control right coronary arteries (RCA) were isolated. Taking the balloon inflation region as a reference, we isolated the proximal and distal LAD areas, performing histological staining and immunohi…
Nitric oxide mediates abnormal responsiveness of thyroid arteries in methimazole-treated patients.
Objective: We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients. Design and methods: Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension. Results and conclusions: Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD2 (−log EC50) values were 7.68±0.19 in…
Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens
We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced con…
U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade.
Objective: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A2 (TXA2), on the adrenergic responses in human saphenous vein. Methods: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. Results: U-46619 (10−10–3×10−7 mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10−10 mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration–response curve for noradrenaline. The TXA2 receptor antagonist SQ-…
Accumulation of Symmetric Dimethylarginine in Hepatorenal Syndrome
In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and l-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 ± 0.25 vs. 0.38 ± 0.06 and 0.29 ± 0.04 μM, respectively; P < 0.05). ADMA and NOx concentrations were…
Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels
Abstract Background . Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. Methods . Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was…
Contractile hyporesponsiveness to norepinephrine of forearm veins in chronic renal failure.
Background We recently reported that endothelium-dependent relaxation is impaired in forearm veins from patients with chronic renal failure. However, assessment of responses to norepinephrine remains controversial. We examined the contractile response to norepinephrine in forearm veins from patients on chronic hemodialysis and the role of nitric oxide (NO), prostanoids, and Ca 2+ -activated K + channels in this response. Methods Isometric contraction curves were obtained in rings of forearm vein from 21 dialyzed patients and 12 multiorgan donors in response to norepinephrine (1 nmol/L to 10 μmol/L) or KCl (5 to 100 mmol/L). Results Veins from uremic patients were markedly less responsive to…
The Role of Chemokines in Alzheimer's Disease
Objective: The most common multifactorial neurodegenerative disorder occurring in old age is Alzheimer’s disease. The neuropathological hallmarks of that disorder are amyloid plaques with the presence of β -amyloid aggregates, intraneuronal tau protein tangles, and chronic inflammation. Brain cells such as microglia and astrocytes are inflammatory cells associated with Alzheimer’s disease and involved in the production of inflammatory mediators, such as cytokines and chemokines. Chemokines consist of a large family of protein mediators with low molecular weight, which able to control the migration and residence of all immune cells. In pathological conditions, such as Alzheimer’s disease, c…
Increased contraction to noradrenaline by vasopressin in human renal arteries
Arginine vasopressin (AVP) not only acts directly on blood vessels through vasopressin V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments. The aim of the present study was to assess whether subpressor concentrations of AVP could contribute to an abnormal adrenergic contractile response of human renal arteries.Renal artery rings were obtained from 27 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension.AVP (10(-10) mol/l) and the vasopressin V1 receptor agonist [Phe2, Orn8]-vasotocin (10(-10) mol/l) produced a leftward shift of the concentration-response curve to noradrenaline (half-…
Increased responsiveness of human pulmonary arteries in patients with positive bronchodilator response.
Abstract 1. The effects of noradrenaline, endothelin-1, acetylcholine and sodium nitroprusside were studied in isolated pulmonary arteries obtained from 14 patients undergoing lobectomy for lung carcinoma. Seven patients had shown increased response to a bronchodilator test prior to operation. In the remaining patients (control) the bronchodilator test was negative. 2. Artery rings from patients with a positive bronchodilator response showed greater contraction to noradrenaline (pD2 = 6.44 +/- 0.1; Emax = 93 +/- 9% of response to 100 mM KCl) and endothelin-1 (pD2 = 8.92 +/- 0.1; Emax = 130 +/- 16%) than the rings from control patients (pD2 = 6.04 +/- 0.08; Emax = 56 +/- 8% for noradrenaline…
Effects of antidepressants in adrenergic neurotransmission of human vas deferens
Objectives. To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. Methods. Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. Results. Amitriptyline caused c…
Role of Ca2+-activated K+ channels and Na+,K+-ATPase in prostaglandin E1- and E2-induced inhibition of the adrenergic response in human vas deferens
We studied the role of K(+) channels and Na(+),K(+)-ATPase in the presynaptic inhibitory effects of prostaglandin E(1) (PGE(1)) and PGE(2) on the adrenergic responses of human vas deferens. Furthermore, we determined the effects of increasing extracellular K(+) concentrations ([K(+)](o)) and inhibition of Na(+),K(+)-ATPase on neurogenic and norepinephrine-induced contractile responses. Ring segments of the epididymal part of the vas deferens were taken from 45 elective vasectomies and mounted in organ baths for isometric recording of tension. The neuromodulatory effects of PGEs were tested in the presence of K(+) channel blockers. PGE(1) and PGE(2) (10(-8) to 10(-6)M) induced inhibition of …
Relaxation induced by milrinone and rolipram in human penile arteries and veins
Abstract We studied the relaxant effects of milrinone, an inhibitor of phosphodiesterase 3, and rolipram, an inhibitor of phosphodiesterase 4, on contracted human penile dorsal artery and deep dorsal vein. Vascular rings from 12 multi-organ donors were suspended in organ baths for isometric recording of tension. Both milrinone and rolipram inhibited (100%) the contraction induced by noradrenaline and shifted the relaxation–response curves to the cAMP forming agents prostaglandin E1 and forskolin to the left. The findings indicate that the cAMP pathway appears to be a main determinant of relaxation in human penile vessels.
Endothelium-dependent responses in human isolated thyroid arteries from donors
The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect w…