Influence of nifedipine on pressor responses induced by different alpha-adrenoceptor agonists and angiotensin II in pithed diabetic hypertensive rats

Objective Both intracellular and extracellular sources of calcium are involved in the activation of contraction in vascular smooth muscle. In the diabetic or hypertensive state, or both, changes induced in calcium handling by various types of agonists may vary considerably. Methods We investigated in which manner L-type calcium-channel blockade with nifedipine influences the presser effects of the alpha(1)-adrenoceptor agonists cirazoline and ST 587, the alpha(2)-adrenoceptor agonist UK 14.304 and angiotensin II, all exerting a differential influence on calcium homeostasis, in pithed spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats rendered diabetic by an injection of 55 mg/kg streptozotocin. Results In diabetic WKY rats and SHR, the maximal presser response was impaired for all agonists, The hypertensive state enhanced the maximal presser response to all agonists, No difference was found in the nifedipine-induced depression of the presser response to cirazoline and angiotensin II in the four groups of rats. The maximal presser responses to ST 587 and UK 14.304 were more effectively depressed by administration of 0.3 mg/kg nifedipine both diabetic WKY rats and in diabetic SHR than they were in their non-diabetic controls. Conclusions Hypertension was associated with enhanced presser response, whereas the diabetic state counteracted this effect. The presser responses in pithed diabetic and diabetic hypertensive rats were clearly more dependent on the nifedipine-sensitive calcium influx than were those in their non-diabetic controls.