Enhanced contractile responses of arteries from diabetic rats to α₁-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 α-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 α₁-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 α₂-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 α-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 α-adrenoceptor agonists are mediated by α₁ 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.