Differential effects of alpha 1- and alpha 2-adrenoceptor agonists on peripheral vasoconstriction in pithed diabetic...

The pressor responses to selective alpha 1-adrenoceptor agonists (cirazoline and methoxamine) and to alpha 2-adrenoceptor agonists (UK-14,304 and B-HT 933) were investigated in pithed, streptozotocin-induced diabetic rats and age-matched control animals. Three months after induction of diabetes, the basal values of diastolic blood pressure (DBP) were the same in pithed diabetic and control rats (34.3 +/- 4.4 vs. 32.8 +/- 4.4 mm Hg, p greater than 0.05, n = 30). In pithed diabetic rats, dose-response curves for the vasoconstrictor effects of cirazoline and methoxamine were shifted to the right with a slight decrease in the maximum response as compared with those in control animals. In contrast, no shift in dose-response curves for the alpha 2-adrenoceptor-mediated vasoconstrictor effects was observed, as reflected by similar pD2 values. A pronounced decrease in the maximum pressor response to the alpha 2-adrenoceptor agonists could be demonstrated. This reduction was significantly greater than that of the alpha 1-adrenoceptor agonists. In conclusion, the functional role of alpha 1- and alpha 2-adrenoceptors in the peripheral resistance vessels appears to be differentially influenced by the diabetic state.