Changes in the responsiveness to endothelin-1 in isolated atria from diabetic rats.
This study investigates the influence of diabetes on the cardiac responsiveness to endothelin-1. The effects of endothelin-1 on rate and force of contraction were examined in isolated right and left atria, respectively, obtained from either streptozotocin (65 mg/kg)-treated rats (diabetic) or vehicle (0.02 M citric acid)-treated rats (control). The positive chronotropic and inotropic effects of endothelin-1 did not change in atria from diabetic rats at 2 and 4 weeks, but were reduced at 8 and 12 weeks. The positive chronotropic response to noradrenaline, but not to sympathetic nerve stimulation, was also reduced in 12-week diabetic rats. Endothelin-1 caused a decrease in the positive chronotropic and inotropic responses to sympathetic nerve stimulation and to noradrenaline; these inhibitory effects of endothelin-1 were not altered in 2-, 4-, 8- or 12-week diabetic rats. The study demonstrates that atrial responses to endothelin-1 and to noradrenaline are reduced by streptozotocin-induced diabetes, but the alteration depends on the duration of diabetes.
Lieu
A T
AT
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Reid
J J
JJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D016232:Endothelins; D009638:Norepinephrine