Pertussis toxin-sensitive G-proteins and regulation of blood pressure in the spontaneously hypertensive rat

1. Increased Gi-protein-mediated receptor-effector coupling in the vasculat ure of the spontaneously hypertensive rat (SHR) has been proposed as a cont ributing factor in the maintenance of elevated blood pressure, If increased Gi-protein-mediated activity plays an important role in hypertension in SH R, then inhibition of Gi-proteins by pertussis toxin would be expected to d ecrease blood pressure in this genetic hypertensive model. To address this hypothesis, studies were undertaken comparing the cardiovascular effects of pertussis toxin in SHR and normotensive Wistar-Kyoto (WKY) rats, 2, Spontaneously hypertensive and WKY rats were instrumented with radiotele metry devices and blood pressure measurements were recorded in conscious ra ts, Following a single injection of pertussis toxin (10 mu g/kg, i.v.), mea n arterial blood pressure fell from 161+/-3 to 146+/-1 mmHg in the SHR and the effect was sustained for more than 2 weeks. In contrast, 10 mu g/kg, i. v., pertussis toxin produced no significant effect on blood pressure in WKY rats (103+/-4 vs 101+/-5 mmHg). 3, In a separate study, SHR and WKY rats were administered 30 mu g/kg, i.v. , pertussis toxin or 150 mu L/kg, i.v., saline and, 3-5 days later, rats we re anaesthetized and instrumented to permit measurement of blood pressure a nd renal function. At this higher dose, pertussis toxin reduced blood press ure in both strains of rat, although the effect was markedly greater in SHR (approximately 40 mmHg decrease) compared with WKY rats (approximately 15 mmHg decrease), In SHR, pertussis toxin increased renal blood dow (from 5.7 +/-0.3 to 7.5+/-0.8 ml/min per g kidney) and decreased renal vascular resis tance (from 31+/-2 to 19+/-2 mmHg/mL per min per g kidney). In WKY rats, pe rtussis toxin had no significant effect on renal parameters. 4, Results from these studies indicate that a pertussis toxin-sensitive Gi- protein-mediated pathway contributes to the maintenance of hypertension and elevated renal vascular tone in the SHR.