Search results for "Prostacyclin"
showing 10 items of 60 documents
Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.
2009
Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modi…
Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide
2012
The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabet…
Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling p…
2014
One of the most important physiological platelet inhibitors is endothelium-derived prostacyclin which stimulates the platelet cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-signaling cascade and inhibits virtually all platelet-activating key mechanisms. Using quantitative mass spectrometry, we analyzed time-resolved phosphorylation patterns in human platelets after treatment with iloprost, a stable prostacyclin analog, for 0, 10, 30, and 60 seconds to characterize key mediators of platelet inhibition and activation in 3 independent biological replicates. We quantified over 2700 different phosphorylated peptides of which 360 were significantly regulated upon stimulation. This com…
Molecular Proteomics and Signalling of Human Platelets in Health and Disease
2021
Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles are tightly regulated by a complex network of signalling pathways. Mass spectrometry-based proteomic techniques are contributing not only to the identification and quantification of new platelet proteins, but also reveal post-translational modifications of these molecules, such as acetylation, glycosylation and phosphorylation. Moreover, target proteomic analysis of platelets can provide molecular biomarkers for genetic aberrations with established or non-established links to platelet dysfunctions. In this report, we review …
Reciprocal regulation of human platelet function by endogenous prostanoids and through multiple prostanoid receptors
2014
Platelets are permanently exposed to a variety of prostanoids formed by blood cells or the vessel wall. The two major prostanoids, prostacyclin and thromboxane act through well established pathways mediated by their respective G-protein coupled receptors inhibiting or promoting platelet aggregation accordingly. Yet the role of other prostanoids and prostanoid receptors for platelet function regulation has not been thoroughly investigated. We aimed at a comprehensive analysis of prostanoid effects on platelets, the receptors and pathways involved and functional consequences. We analyzed cAMP formation and phosphorylation of proteins pivotal to platelet function as well as functional platelet…
Increased Platelet Sensitivity toward Platelet Inhibitors during Physical Exercise in Patients with Coronary Artery Disease
1999
Generalized atherosclerosis and coronary artery disease (CAD) are associated with endothelial dysfunction and during acute myocardial ischemia platelet activation has been reported. Activated platelets exert activated fibrinogen receptors (GP IIb/IIIa) and express CD 62p being regarded as reliable marker for platelet activation. Patients with angiographically proven CAD performed a bicycle exercise test until the onset of angina or ST-segment depression. We studied the ischemia-induced alterations in fibrinogen binding to activated platelet GP IIb/IIIa receptors and CD 62p expression. Therefore, the basal fibrinogen binding to GP IIb/IIIa and CD 62p expression and the thrombin-concentration…
Synergistic Platelet Inhibitory Effect of the Phosphodiesterase Inhibitor Piroximone and Iloprost
1992
Platelet activity is regulated through synthesis and degradation of the intracellular second messengers cAMP or cGMP. The antiplatelet effect of the phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50 of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of platelet count following injection of 100 micrograms/kg bw collagen was measured after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in …
Influence of experimental diabetes on regulatory mechanisms of vascular response of rabbit carotid artery to acetylcholine
2000
Summary The purpose of this study was to analyse the influence of experimental diabetes on vascular response of rabbit carotid artery to acetylcholine (Ach). We compared the Ach-induced relaxant response of isolated arterial segments obtained from both control and diabetic animals. To assess the influence of the endothelium, this cell layer was mechanically removed in some of the arterial segments (“rubbed arteries”) from each experimental group. Ach induced a concentration-related endothelium-mediated relaxation of carotid artery from control rabbits that was significantly higher with respect to that obtained in diabetic animals. Pre-treatment with NG-nitro-L-arginine (L-NA) induced a conc…
Increased Circulating Levels of 3-Nitrotyrosine Autoantibodies
2012
3-nitrotyrosine formation is an oxidative protein modification that was first discovered in vivo in the early 1990s by Beckman and colleagues.1,2 The biological relevance of this process was extensively investigated in the subsequent years and further facilitated by the development of 3-nitrotyrosine–specific antibodies.3 Protein tyrosine nitration is mainly mediated by 3 biochemical processes (Figure): (1) by peroxynitrite (ONOO−) formation,4–6 the reaction product of nitric oxide (•NO) and superoxide (•O2−); (2) by a (myelo)peroxidase-catalyzed nitrogen dioxide radical (•NO2) formation from hydrogen peroxide and nitrite;7,8 and (3) by a nonspecific formation of the nitrogen dioxide radica…
Inhaled Prostacyclin, Nitric Oxide, and Nitroprusside in Pulmonary Hypertension After Mitral Valve Replacement
2005
Abstract Objective: Pulmonary hypertension increases morbidity and mortality in patients undergoing heart surgery. Mitral valve stenosis is frequently associated with an increase in pulmonary vascular resistance (PVR). Cardiopulmonary bypass exacerbates pulmonary hypertension in patients undergoing cardiac surgery. The aim of this study was to compare the hemodynamic effects of inhaled prostacyclin and nitric oxide and the administration of i.v. nitroprusside during cardiac surgery with a clinical, pharmacodynamic dose-response, prospective, randomized, and double-blind study (Group A: inhaled prostacyclin; Group B: inhaled nitric oxide; Group C: nitroprusside). Materials and Methods: Fifty…