Insulin and vanadate restore decreased plasma endothelin concentrations and exaggerated vascular responses to normal in the streptozotocin diabetic rat.
Although insulin has been shown to raise plasma concentrations of endothelin (ET) and up regulate vascular smooth muscle ETA receptor expression, the interaction of vanadate, an insulinomimetic agent, with the vascular ET system has not been investigated. We compared the effects of oral vanadate treatment (0.5 mg/ml; p.o.) and insulin infusion (12 mU.kg-1.min-1 s.c.) for two weeks on plasma ET concentrations and vascular responses to endothelin-1 (ET-1) and the alpha-1 adrenoceptor agonist, methoxamine, in aortic ring preparations from streptozotocin (STZ) diabetic and non-diabetic adult male Sprague-Dawley rats. Plasma ET concentrations were lower (p < 0.01) in STZ diabetic rats compared with normal control rats. Insulin and vanadate treatment restored plasma ET to normal (p < 0.01) in STZ rats and increased ET concentrations in the control (p < 0.05) group. Higher maximal tension responses to both ET-1 (p < 0.01) and methoxamine (p < 0.05) were present in STZ rats in both endothelium intact and denuded aortic preparations compared with the control group. Both insulin and vanadate treatment returned these responses to normal. It is concluded that low plasma concentrations of insulin and high plasma glucose in STZ diabetic rats are accompanied by lower concentrations of plasma ET. Insulin and vanadate treatment restores diminished plasma ET to control concentrations and attenuates exaggerated agonist(s)-evoked vascular smooth muscle responses in STZ-induced diabetic rats. In addition to well known beneficial metabolic effects, insulin and vanadate may beneficially affect cardiovascular regulation in the STZ diabetic rat by correcting abnormal ET activity.
Hopfner
R L
RL
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Misurski
D
D
Wilson
T W
TW
McNeill
J R
JR
Gopalakrishnan
V
V
D000818:Animals; D001011:Aorta; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D019332:Endothelin-1 / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001786:Blood Glucose; D019332:Endothelin-1; D007328:Insulin; D014662:Vasoconstrictor Agents; D014638:Vanadates; D008729:Methoxamine