Human insulin-mediated enhancement of vascular beta-adrenergic responsiveness.
Insulin may play an important role in the physiological and/or pathophysiological regulation of the cardiovascular system. Defects in insulin secretion and insulin receptor responsiveness have been associated with increased peripheral resistance and hypertension. The mechanisms linking these events remain unclear. To assess the effect of insulin on beta-adrenergic-mediated vasodilation, we examined aortic ring segments obtained from normotensive male Wistar and spontaneously hypertensive rats. Vessels were maximally preconstricted with phenylephrine (3 mumol/L). Relaxation was induced by either isoproterenol (10 mumol/L) or sodium nitroprusside (10 nmol/L), and the relaxant response was followed for 20 minutes. Insulin exposure did not alter phenylephrine-mediated constriction. However, insulin mediated a dose-dependent increase in isoproterenol-induced relaxation, to a maximum of 120 +/- 4% of baseline isoproterenol-mediated relaxation, with an EC50 for insulin of 32 pmol/L in aortic rings from Wistar rats. Insulin exposure also did not alter nitroprusside-mediated relaxation. In contrast to the results obtained in rings from Wistar rats, insulin did not enhance isoproterenol-mediated responses in rings from spontaneously hypertensive rats. Thus, insulin mediates a selective enhancement of vascular beta-adrenergic responsiveness in aortas from normotensive but not hypertensive animals.
Gros
R
R
Department of Medicine, University of Western Ontario, London, Canada.
Borkowski
K R
KR
Feldman
R D
RD
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D007545:Isoproterenol