EFFECTS OF PERTUSSIS AND CHOLERA TOXINS ON ALPHA-ADRENOCEPTOR FUNCTION IN RAT TAIL ARTERY - DIFFERENCES IN HYPERTENSION

The alpha(1)- and alpha(2)-adrenoceptor-stimulated contractile respons es of rat tail artery rings were compared in Sprague-Dawley (SD), spon taneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were un treated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an alpha(2)-adrenoceptor agonist) and cirazoline (a selecti ve alpha(1)-adrenoceptor agonist) were significantly greater in SHR th an in SD or WKY, and the tissues were more sensitive to the agonists i n SHR or SD than in WKY. Yohimbine (0.1 mu M), a selective alpha(2)-ad renoceptor antagonist, shifted the dose-response curves fdr clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 mu M), a selective alpha(1)-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were n ot different among these three strains of rats. Nifedipine (0.05 mu M) completely blocked the response to clonidine in SD and WKY; however, in SHR, approximately one-third of the response to clonidine was resis tant to nifedipine. Nifedipine, at 0.05 mu M, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 mu g/kg, 3 days before experiment) almost completely blocked the responses to cl onidine, but only partially inhibited those to cirazoline. After pertu ssis toxin pretreatment, the responses (maximal effects and EC(50)s) t o clonidine and cirazoline were not significantly different in arterie s from the three strains of rats. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induce d by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses indu ced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the m aximal responses to alpha(1)- and alpha(2)-adrenoceptor agonists are e nhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tis sues from WKY; (iii) responses to clonidine, but not cirazoline, in ti ssues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera to xin is involved in the regulation of both alpha(1)- and alpha(2)-adren oceptor signal transduction processes in rat tail artery smooth muscle ; and (v) pretreatment with pertussis toxin reduces the enhanced respo nse levels of SHR tissues so that the maximal contractile responses to both alpha(1)- and alpha(2)-adrenoceptor agonists are equivalent in a rteries from the three strains of rats.