Effect of diabetes on vascular smooth muscle function in normotensive and spontaneously hypertensive rat mesenteric artery.
We have examined the functional responses to alpha-adrenoceptor agonists (alpha 1-selective: methoxamine and phenylephrine; alpha 2-selective: clonidine and B-HT 920; non-selective: norepinephrine, serotonin and K+ in ring segments of mesenteric artery of control and streptozotocin-induced diabetic spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Systolic blood pressure and contractile responses were examined after 12 weeks of diabetes. There was no significant change in the diabetic WKY rats as compared with the control WKY rats. However, diabetic SHR had significantly less hypertension than control SHR. Responses to serotonin and alpha 2-adrenoceptor agonists were augmented significantly in arteries from control SHR animals as compared with vessels from WKY animals. There was no significant difference in the force of contraction generated by other agonists in both nondiabetic groups. Responses to all agonists in WKY diabetic and to methoxamine and K+ in SHR diabetic arteries were increased as compared with their respective controls. ED50 values for each agonist were similar in all groups. Indomethacin (5 microM) shifted the dose-response curve to norepinephrine to the right in arteries from all groups of animals. However, in the diabetic SHR and WKY, there was a significant reduction in norepinephrine maximum response. Nifedipine was more potent in inhibiting the contraction to K+ and serotonin in WKY diabetic arteries as compared with WKY controls. However, nifedipine inhibited the responses to all agonists with equal potency in the control and diabetic SHR vessels. These results suggest the involvement of alpha 2-adrenoceptors and serotonin receptors in the development and (or) the maintenance of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Agrawal
D K
DK
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
McNeill
J H
JH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001786:Blood Glucose; D009543:Nifedipine; D007213:Indomethacin