Vascular responses to agonists in rat mesenteric artery from diabetic rats.
The effect of diabetes on vascular smooth muscle function was investigated in the muscular arteries from spontaneously and chemically induced diabetic rats. Isolated ring segments of superior mesenteric arteries from BB diabetic and streptozotocin (STZ)-diabetic rats (12 weeks after onset of diabetes) were used for isometric tension studies. Contractile responses to alpha-adrenoceptor agonists (norepinephrine, methoxamine, phenylephrine, B-HT 920, guanabenz, SKF 89748-A), serotonin, and K+ were significantly higher in STZ-diabetic rat arteries as compared with the controls. In spontaneously diabetic rat arteries only the contractile responses to the putatively selective alpha 2-adrenoceptor agonists, K+ and prostaglandin E1, were significantly increased. pD2 values of the agonists in both groups of diabetic arteries were not significantly different from the respective controls. Nifedipine inhibited all contractile responses in a dose-dependent fashion. The responses to K+ and alpha 2-adrenoceptor agonists were attenuated to a greater extent by nifedipine in both groups of diabetic blood vessels. The calcium channel activator, BAY K 8644, produced a twofold increase in force of contraction in streptozotocin-diabetic and spontaneously diabetic rat arteries as compared with the responses in their respective controls. These results suggest caution in extrapolating all the findings from the streptozocin-induced diabetic model to the spontaneously diabetic model. However, increased activity of calcium channels in vascular muscle cells in both groups of diabetics may be responsible, at least in part, for the increased vascular contractility in diabetes mellitus.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D010656:Phenylephrine; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008729:Methoxamine; D009543:Nifedipine; D011188:Potassium; D009638:Norepinephrine