0000000000846148
AUTHOR
Salvador Lluch
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…
Contractile effects of arginine analogues on human internal thoracic and radial arteries
Abstract Objectives: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. Results: N G -monomethyl L -arginine (10 –6 to 10 –3 mol/L) and N G ,N G -dimethyl L -arginine (10 –6 to 10 –3 mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contracti…
Basal release of nitric oxide in the mesenteric artery in portal hypertension and cirrhosis: Role of dimethylarginine dimethylaminohydrolase
Background and Aim Increased basal release of nitric oxide (NO) in the splanchnic circulation contributes to elevated plasma levels of NO observed in decompensated cirrhosis. We evaluated in rat mesenteric arteries whether the differences in basal release of NO, revealed by asymmetric dimethylarginine (ADMA)- and NG-nitro-L-arginine methyl ester (L-NAME)-induced contractions, were associated with changes in messenger RNA (mRNA) expression of endothelial NO synthase (eNOS) and dimethylarginine dimethylaminohydrolases (DDAHs). Methods Rat small mesenteric arteries from 14 Sham-control, from 14 with partial portal vein ligation (PPVL), and from 14 with bile duct excision (BDE)-induced cirrhosi…
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…
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…
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…
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…
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…
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…
Oxidative and Nitrosative Pattern in Circulating Leukocytes of Very Early/Early Hepatocellular Carcinoma Patients
Background/aim In chronic liver disease, various immune cell subsets exert pro or anti-tumour effects by releasing reactive oxygen and nitrogen species (ROS, RNS). Here, we evaluated the oxidative and nitrosative pattern in peripheral blood leukocyte subpopulations of early hepatocellular carcinoma (HCC) patients compared with HCC-free cirrhotic patients. Materials and methods Venous blood samples from 18 HCC-free cirrhotic patients and 17 early stage HCC patients were collected to determine ROS, RNS and reduced glutathione levels in isolated leukocytes analyzed by flow cytometry. Results Intracellular levels of ROS and glutathione were higher in lymphocytes, monocytes, and neutrophils from…
Endothelin action on goat cerebral arteries.
Abstract Cumulative application of endothelin-1 (human) markedly constricted goat isolated cerebral arteries in a concentration-dependent manner. Contractile responses were not affected by removal of endothelial cells. Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−7 M) failed to abolish responses to endothelin. The results suggest that the endothelium-independent constriction of cerebral arteries produced by endothelin cannot be explained solely by voltage-dependent calcium channels. The contractile responses are likely to be mediated by stimulation of specific receptors for this peptide.
Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery
1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms dura…
4-Hydroxynonenal-Induced Relaxation of Human Mesenteric Arteries1
The effect of 4-hydroxynonenal (4-HNE), a circulating lipid peroxidation product, on the vascular tone of human mesenteric arteries is studied. 4-HNE promotes relaxation of human mesenteric arterial rings in a concentration-dependent manner. Removal of the endothelium or treatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10(-4) M) partially prevented 4-HNE-induced relaxation, thus suggesting the intervention of nitric oxide from endothelial origin in the vascular effects of 4-HNE.
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…
Relaxant effects of antidepressants on human isolated mesenteric arteries
Aims The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. Methods Arterial segments (lumen diameter 0.8–1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operat…
Enhancement by vasopressin of adrenergic responses in human mesenteric arteries.
Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited…
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…
Nitric oxide mediates abnormal responsiveness of thyroid arteries in methimazole-treated patients
Objective: We studied the intervention of nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid (E) and methimazole-treated (MT) patients. Design and methods: Branches of the superior thyroid artery were obtained from 19 E 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 7.68±0.19 in E and 8.17±0.26 in M…
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…
Endothelium-independent contractions of human cerebral arteries in response to vasopressin.
We studied the effects of vasopressin in isolated segments from branches (500-700 micrograms in external diameter) of human middle cerebral arteries obtained during autopsy of 15 patients who had died 3-8 hours before. Paired segments, one normal and the other de-endothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. In 11 normal segments, vasopressin produced concentration-dependent contractions with an EC50 of 7.0 X 10(-10) M. Removal of the endothelium from 12 segments did not significantly affect vasopressin-induced contractions. Vasopressin produced further contractions in arterial segments with (n = 4) or without (n = 5) endothelium precontract…
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…
Effects of vasopressin on human renal arteries
The effects of vasopressin were studied in isolated rings from branches (2-3 mm in external diameter) of human renal arteries obtained from 18 patients undergoing nephrectomy for non-obstructive neoplasia. In arterial rings under resting tension, vasopressin produced concentration-dependent and endothelium-independent contractions with an EC 50 of 9.1 x 10 -10 mol L -1 . The vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 -6 mol L -1 ) displaced the control curve to vasopressin 564-fold to the right in a parallel manner. In precontracted arterial rings and previously treated with the V 1 antagonist (10 -6 mol L -1 ) vasopressin caused endothelium-independent relaxation. The re…
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…
Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries
Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not abolish responses to endothelin. These experiments show that the endothelin-induced contraction in human cerebral arteries is not linked to the presence of intact endothelial cells. The data also show that the contractile effects of endothelin cannot be explained solely by an action on voltage-dependent calcium channels.
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 …
Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries.
The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine meth…
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-…
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…
4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries.
The relaxant effect of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, on human cerebral arteries was studied. Addition of 4-HNE to artery rings promoted no contraction, and after stimulation with prostaglandin F2α (PFG2α; 10−7-3 × 10−6 M), 100% relaxation was obtained with 3 × 10−5 M 4-HNE. Inhibition of nitric oxide formation with NG-nitro-l-arginine methyl ester hydrochloride (l-NAME; (10−4 M), as well as prostaglandin synthesis with indomethacin (3 × 10−6 M), partially prevented 4-HNE-induced relaxation, but each of these substances separately failed to inhibit complete relaxation. Addition of both inhibitors together reduced 4-HNE-induced relaxation to ≈50%, but relaxation cou…
Relaxation of human isolated mesenteric arteries by vasopressin and desmopressin.
1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the…
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…
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…
Contractile Response of Human Omental Arteries to Endothelin
Abstract The effects of endothelin have been studied in isolated arterial segments (0·8–1 mm in external diam.) of human omental arteries obtained during the course of abdominal operations (15 patients, 7 men and 8 women). Paired segments, one normal and the other de-endothelized, were mounted for isometric recording of tension in organ baths. Endothelin produced concentration-dependent contractions with an EC50 value of 5·4 × 10−9 m. Removal of endothelium did not affect significantly endothelin-induced contractions (EC50, 6·7 × 10−9 m). Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−6 m) diminished but did not abolish responses to endothelin…
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 …
Unchanged plasma levels of dimethylarginines and nitric oxide in chronic hepatitis C.
Previous studies have shown that asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and nitric oxide (NO) play a prominent role in liver dysfunction. The objective of this study was to determine whether plasma levels of ADMA, SDMA and NO are altered in patients with chronic hepatitis C.Plasma levels of ADMA, SDMA and NO (nitrite plus nitrate) were measured in 22 patients with chronic hepatitis C and 24 patients with sustained virologic response after treatment with peginterferon plus ribavirin. Seven healthy volunteers served as controls.Plasma levels of ADMA, SDMA and NO were not significantly different between groups: chronic hepatitis C, ADMA 0.55+/-0.06, SDMA 0.22+/-0…
NG-monomethyl-L-arginine and NG-nitro-L-arginine inhibit endothelium-dependent relaxations in human isolated omental arteries.
Abstract The L-arginine analogues NG-monomethyl-l-arginine (l-NMMA, 10−4 m) and NG-nitro-L-arginine methyl ester (l-NAME, 10−4 m), which specifically inhibit the synthesis of nitric oxide from l-arginine, significantly reduced acetylcholine-induced endothelium-dependent relaxations in rings of human omental arteries. The inhibitory potency of l-NMMA and l-NAME was similar. Addition of l-NMMA or l-NAME to the organ bath did not induce any significant changes in the resting tension of the tissues. The effects of l-NMMA were reversed by l-arginine (3 × 10−4 m). The l-NMMA enantiomer, d-NMMA (10−4 m), did not influence either the basal tone of the preparation or the relaxing effects of acet…
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…
Comparative effects of dilator drugs on human penile dorsal artery and deep dorsal vein
The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 ;mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and ana…