Enhanced contractile responses of arteries from diabetic rats to alpha 1-adrenoceptor stimulation in the absence and presence of extracellular calcium.
The purpose of this study was to determine the receptor subtype mediating enhanced contractile responses of aortae and mesenteric arteries from diabetic rats to the alpha-adrenoceptor agonists, norepinephrine, clonidine, and methoxamine and to establish whether the enhanced responses are associated with increased release of intracellular Ca2+ or are dependent on the presence of extracellular Ca2+. The pA2 values calculated for the alpha 1-selective antagonist prazosin were similar in arteries from control and diabetic rats and were 2.5-3 log units greater than pA2 values calculated for the alpha 2-selective antagonist yohimbine. Contractile responses of aortae incubated in Ca2(+)-free Krebs' solution containing 1 mM EGTA to maximal but not to ED50 concentrations of the alpha-adrenoceptor agonists were significantly greater in preparations from diabetic than from control rats. Following readdition of Ca2+, contractile responses of diabetic aortae to all concentrations of the agonists tested were significantly greater than control. Similar results were obtained in mesenteric arteries, except that no clonidine response could be detected in preparations from either diabetic or control rats in the absence of extracellular Ca2+. These data indicate that enhanced responses of arteries from diabetic rats to alpha-adrenoceptor agonists are mediated by alpha 1 adrenoceptors, and are largely dependent on the presence of extracellular Ca2+. However, increased release of intracellular Ca2+ appears to contribute to enhanced responses to high concentrations of these agonists.
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
W
W
Abebe
K H
KH
Harris
K M
KM
MacLeod
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D015016:Yohimbine; D008729:Methoxamine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin