Calcium‐dependence and antagonism of responses to α₁‐ and α₂‐adrenoceptor agonists in vascular tissues from hypertensive and normotensive rats

Inhibition by D600 (methoxyverapamil) of responses to an α₂‐adrenoceptor selective agonist, B‐HT 920, (6‐allyl‐2‐amino‐5, 6, 7, 8‐tetrahydro‐4H‐thiazolo [4, 5‐d] azepin dihydrochloride), an α₁‐adrenoceptor selective agonist, phenylephrine (PE), and a nonselective agonist, noradrenaline (NA), was studied in isolated preparations of the aortae and carotid arteries obtained from young (5–7 weeks) and old (15–17 weeks) hypertensive (SHR) and normotensive (WKY) rats. Maximum responses of WKY tissues to B‐HT 920 were the most sensitive, PE‐induced responses the least sensitive and maximum responses to NA were intermediate in their sensitivity to inhibition by D600. Sub‐maximal responses to NA and PE were not different in their sensitivity to inhibition by D600, but were less sensitive than the responses to B‐HT 20. Sub‐maximal responses to PE were significantly more sensitive to D600 inhibition than were the maximal responses to this agonist. NA‐induced responses of tissues from older SHR were less sensitive to inhibition by D600 when compared to responses in WKY rats. Responses to B‐HT 920, in tissues suspended in calcium‐free solutions, showed the largest decline compared to NA‐ and PE‐induced responses. We conclude that responses to B‐HT 920 largely utilize extracellular calcium. PE‐ and NA‐induced responses mobilize extracellular calcium to varying degrees depending upon the concentration of the agonist employed to elicit the response. 1984 British Pharmacological Society