Endothelin-1 Receptor Blockade Prevented the Electrophysiological Dysfunction in Cardiac Myocytes of Streptozotocin-Induced Diabetic Rats

Endocrine ◽  
2006 ◽  
Vol 30 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Yanfeng Ding ◽  
Ruijiao Zou ◽  
Robert L. Judd ◽  
Juming Zhong
Keyword(s):  
Cardiac Myocytes ◽  
Diabetic Rats ◽  
Receptor Blockade ◽  
Endothelin 1

Exaggerated coronary reactivity to endothelin-1 in diabetes: reversal with bosentan

2002 ◽  
Vol 80 (10) ◽  
pp. 980-986 ◽  
Author(s):  
Subodh Verma ◽  
Emi Arikawa ◽  
Sammy Lee ◽  
Aaron S Dumont ◽  
Linfu Yao ◽  
...  
Keyword(s):  
Heart Function ◽  
Coronary Perfusion Pressure ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Coronary Perfusion ◽  
Receptor Blockade ◽  
Endothelin Receptor ◽  
Endothelin 1 ◽  
Streptozotocin Induced Diabetes ◽  
And Control

We previously demonstrated that chronic endothelin receptor blockade (with bosentan) improved functional cardiac performance in streptozotocin-diabetic rats, suggesting a novel role of endothelin-1 (ET-1) in modulating diabetic heart dysfunction. To gain insight into the mechanism(s) underlying this effect, we examined the coronary vascular responses to ET-1 in hearts from diabetic and control rats treated with or without bosentan. Rats were divided into control, control-treated, diabetic, and diabetic-treated groups. The control-treated and diabetic-treated groups received bosentan (100 mg·kg–1·d–1) for 8 weeks. Following treatment, hearts were isolated and perfused, and coronary reactivity to ET-1 was assessed by measuring the changes in coronary perfusion pressure in response to ET-1 (50 and 100 pM). Additionally, maximal coronary blood flow (assessed with 10–5 M adenosine) was measured in isolated perfused hearts. The key observation is that coronary reactivity to ET-1 was significantly higher in the diabetic than the control rats. This effect was normalized in diabetic rats chronically receiving bosentan. Maximal coronary vasodilation did not differ between the four groups. In conclusion, the reactivity of ET-1 is altered in the isolated perfused coronary vascular bed from diabetic rats, and chronic ET receptor blockade restores this reactivity to control values. These observations provide a possible mechanism for the improvement in diabetic heart function observed after chronic bosentan treatment.Key words: endothelin-1, streptozotocin-induced diabetes, bosentan, endothelin receptor antagonist, coronary artery.

scholarly journals Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia

2003 ◽  
Vol 64 (3) ◽  
pp. 962-969 ◽  
Author(s):  
Alejandro R. Chade ◽  
Patricia J. Best ◽  
Martin Rodriguez-Porcel ◽  
Joerg Herrmann ◽  
Xiangyang Zhu ◽  
...  
Keyword(s):  
Renal Injury ◽  
Receptor Blockade ◽  
Endothelin 1 ◽  
Experimental Hypercholesterolemia

Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids

1992 ◽  
Vol 70 (9) ◽  
pp. 1271-1279 ◽  
Author(s):  
Brian Rodrigues ◽  
Janice E. A. Braun ◽  
Michael Spooner ◽  
David L. Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Cardiac Myocytes ◽  
Lipase Activity ◽  
Plasma Lipids ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Lipoprotein Lipase Activity ◽  
Triton Wr 1339 ◽  
Plasma Triacylglycerol

The objective of this investigation was to test the hypothesis that the diabetes-induced reduction in lipoprotein lipase activity in cardiac myocytes may be due to hypertriglyceridemia. Administration of 4-aminopyrazolopyrimidine (50 mg/kg) to control rats for 24 h reduced plasma triacylglycerol levels and increased the heparin-induced release of lipoprotein lipase into the incubation medium of cardiac myocytes. The acute (3–5 days) induction of diabetes by streptozotocin (100 mg/kg) produced hypertriglyceridemia and reduced heparin-releasable lipoprotein lipase activity in cardiac myocytes. Treatment of diabetic rats with 4-aminopyrazolopyrimidine resulted in a fall in plasma triacylglycerol content and increased heparin-releasable lipoprotein lipase activity. Administration of Triton WR-1339 also resulted in hypertriglyceridemia, but the heparin-induced release of lipoprotein lipase from control cardiac myocytes was not reduced in the absence of lipolysis of triacylglycerol-rich lipoproteins. Treatment with Triton WR-1339 did, however, increase the heparin-induced release of lipoprotein lipase from diabetic cardiac myocytes. Preparation of cardiac myocytes with 0.9 mM oleic acid resulted in a decrease in both total cellular and heparin-releasable lipoprotein lipase activities. These results suggest that the diabetes-induced reduction in heart lipoprotein lipase activity may, at least in part, be due to an inhibitory effect of free fatty acids, derived either from lipoprotein degradation or from adipose tissue lipolysis, on lipoprotein lipase activity in (and (or) release from) cardiac myocytes.Key words: diabetes, plasma triacylglycerols, cardiac myocytes, lipoprotein lipase.

Effect of endothelin-1 and endothelin receptor blockade on the release of microparticles

2016 ◽  
Vol 46 (8) ◽  
pp. 707-713 ◽  
Author(s):  
Christian Jung ◽  
Michael Lichtenauer ◽  
Bernhard Wernly ◽  
Marcus Franz ◽  
Bjoern Goebel ◽  
...  
Keyword(s):  
Receptor Blockade ◽  
Endothelin Receptor ◽  
Endothelin 1

Abstract P095: Aerobic Exercise Training Reduces Endothelin-1-mediated Vasoconstriction In Postmenopausal Women

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Megan M Wenner ◽  
Caitlin Dow ◽  
Jared Greiner ◽  
Brian Stauffer ◽  
Christopher Desouza
Keyword(s):  
Exercise Training ◽  
Aerobic Exercise ◽  
Postmenopausal Women ◽  
Exercise Intervention ◽  
Aerobic Exercise Training ◽  
Receptor Blockade ◽  
Maximal Heart Rate ◽  
Endothelin 1 ◽  
Vasodilator Response ◽  
Exercise Induced

Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in postmenopausal women (PMW), contributing to their increased cardiovascular risk. Although aerobic exercise is beneficial in reducing ET-1 system activity in men, it is unknown whether this favorable vascular effect is conferred in women. In fact, contrary to men, it is uncertain whether aerobic exercise training improves endothelial dysfunction in PMW. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW. Methods: Forearm blood flow (FBF) responses to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) in the absence and presence of ET A receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) were determined before and after a 12-week aerobic exercise training intervention in 20 healthy, sedentary PMW (56 + 1 yr). Results: All 20 PMW completed the exercise intervention, walking an average of 4.9 + 0.1 d/wk for 50 + 2 min/d at 71 + 1% of maximal heart rate. After the exercise intervention, BQ-123 elicited no significant change in resting FBF in the previously sedentary PMW compared with significant vasodilation (~25%) before exercise. FBF responses to acetylcholine were markedly higher (~25%; P<0.05) after (from 4.3 + 0.3 to 13.8 + 0.8 mL/100 ml tissue/min) vs before (from 4.1 + 0.2 to 11.3 + 0.8 mL/100 ml tissue/min) exercise training. Moreover, before exercise training the co-infusion of BQ-123 with acetylcholine enhanced (~25%; P<0.05) the vasodilator response (from 4.3 + 0.3 to 13.7 + 0.7 mL/100 mL tissue/min) compared with acetylcholine alone; after exercise training, the presence of BQ-123 did not significantly affect the vasodilator response to acetylcholine. Conclusions: These data demonstrate that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. Furthermore, decreased ET-1-mediated vasoconstriction is an important mechanism underlying aerobic exercise-induced improvement in endothelium-dependent vasodilation in PMW.

Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes

1997 ◽  
Vol 273 (3) ◽  
pp. H1403-H1407 ◽  
Author(s):  
S. Yasuda ◽  
W. Y. Lew
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cardiac Myocytes ◽  
Contractile Function ◽  
Adult Rabbit ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endothelin 1 ◽  
Cardiac Depression ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Lipopolysaccharide (LPS) induces cardiac depression by activating nitric oxide pathways to increase guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide. Endothelin-1 (ET-1) may interact with nitric oxide pathways. We hypothesized that ET-1 modulates LPS-induced contractile depression in cardiac myocytes. Adult rabbit cardiac myocytes exposed to LPS (10 ng/ml) developed decreased cell shortening after 6 h, with an increase in cardiac cGMP levels [606 +/- 36 (SE) fmol/mg protein] compared with control myocytes (360 +/- 26 fmol/mg protein, P < 0.05). LPS effects were completely blocked by coincubation with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (1 mM). Coincubation with ET-1 (10 nM) attenuated the contractile depression and increase in cGMP with LPS (482 +/- 28 fmol/mg protein, P < 0.05 vs. LPS alone). ET-1 alone did not alter cGMP levels (350 +/- 30 fmol/mg protein). ET-1 effects on contractile function were blocked by BQ-123 (10 microM), a selective ET-1 type A receptor antagonist. We conclude that ET-1 ameliorates LPS-induced contractile depression in cardiac myocytes by attenuating LPS effects on nitric oxide-cGMP pathways.

Modulation of transmembrane potential of isolated cardiac myocytes by insulin and isoproterenol

1990 ◽  
Vol 259 (2) ◽  
pp. H554-H559
Author(s):  
J. Eckel ◽  
H. Reinauer
Keyword(s):  
Cardiac Myocytes ◽  
Insulin Action ◽  
Transmembrane Potential ◽  
Cardiac Myocyte ◽  
Potassium Conductance ◽  
Diabetic Rats ◽  
Maximal Effect ◽  
Physiological Concentration ◽  
Adult Rat ◽  
Hormonal Modulation

Isolated muscle cells from adult rat heart have been used to study the effects of insulin and catecholamines on transmembrane potential by following triphenylmethylphosphonium cation uptake. Insulin was found to hyperpolarize the cells with a maximal effect of 3.2 +/- 0.7 mV (n = 4) at an insulin concentration of 3 x 10(-9) mol/l. This insulin action was fully antagonized by isoproterenol (10(-5) mol/l), which depolarized the cardiocytes in a dose-dependent fashion with a maximal effect of 9.5 +/- 2.2 mV. Treatment of cardiocytes with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or CsCl resulted in a total loss of insulin action, whereas isoproterenol action was not affected. Cardiac myocytes from streptozotocin diabetic rats exhibited an unaltered hyperpolarization by insulin within the physiological concentration range. Isoproterenol now induced a biphasic response with a significant hyperpolarization at low doses and a decreased depolarization at maximal concentrations. In conclusion, 1) hormonal modulation of cardiac myocyte membrane potentials involves hyperpolarization by insulin and depolarization by beta-agonists, 2) insulin action appears to be related to an increased potassium conductance and may be antagonized by beta-stimulation, and 3) membrane potential modulation may be profoundly altered in the diabetic state.

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