Effects of in vivo treatment with pertussis and cholera toxins on pressor effects mediated by α-adrenoceptor agonists and vasopressin: Changes in hypertension
Muscle, Smooth, Vascular
The pressor effects of arginine vasopressin, the α1-adrenoceptor agonists cirazoline and St 587, as well as the α2-adrenoceptor agonist B-HT 920 were compared in pithed Sprague-Dawley rats that had been pretreated with either pertussis toxin or normal saline vehicle. Pertussis toxin treatment did not significantly affect the prepithing blood pressure of these animals, nor did it affect the dose-response curve to arginine vasopressin or that to cirazoline; however, there was a significant enhancement of the ED50 values for B-HT 920 and St 587, as well as a significant reduction in the maximum response to these agonists. The effects of cholera toxin on pressor responses to the α-adrenoceptor agonists was also examined, and a shift to the right of the dose-response curves, as well as a depression of the maximum, for cirazoline and St 587 was noted; however, cholera toxin had no effect on responses to B-HT 920. Pertussis and cholera toxin thus differentially affect the pressor actions of α-adrenoceptor agonists. In a comparison of the effects of pertussis toxin on the pressor actions of arginine vasopressin in spontaneously hypertensive versus Wistar-Kyoto rats, however, differences were noted. Thus pertussis toxin pretreatment lowered the prepithing blood pressure and depressed the pressor response to arginine vasopressin of the spontaneously hypertensive but not the Wistar-Kyoto rat. In conclusion, cholera and pertussis toxins may prove to be useful tools in dissecting out changes in G-protein-coupling processes associated with vascular smooth muscle dysfunction in hypertension.