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. I n the diabetic or hypertensive state, or both, changes induced in calc ium handling by various types of agonists may vary considerably. Metho ds We investigated in which manner L-type calcium-channel blockade wit h nifedipine influences the presser effects of the alpha(1)-adrenocept or agonists cirazoline and ST 587, the alpha(2)-adrenoceptor agonist U K 14.304 and angiotensin II, all exerting a differential influence on calcium homeostasis, in pithed spontaneously hypertensive rats (SHR) a nd normotensive Wistar-Kyoto (WKY) rats rendered diabetic by an inject ion of 55 mg/kg streptozotocin. Results In diabetic WKY rats and SHR, the maximal presser response was impaired for all agonists, The hypert ensive state enhanced the maximal presser response to all agonists, No difference was found in the nifedipine-induced depression of the pres ser response to cirazoline and angiotensin II in the four groups of ra ts. The maximal presser responses to ST 587 and UK 14.304 were more ef fectively depressed by administration of 0.3 mg/kg nifedipine both dia betic WKY rats and in diabetic SHR than they were in their non-diabeti c controls. Conclusions Hypertension was associated with enhanced pres ser response, whereas the diabetic state counteracted this effect. The presser responses in pithed diabetic and diabetic hypertensive rats w ere clearly more dependent on the nifedipine-sensitive calcium influx than were those in their non-diabetic controls.