In a comparison of the spontaneously hypertensive rat (SHR) with Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats, it was shown that pertussis toxin (PTX) lowers the blood pressure of the SH but not WKY or SD rats. Sympathetic nerve stimulation (SNS), via the pithing rod, the nitric oxide NO)-synthase inhibitor NW-Nitro-L-arginine methyl ester L-NAME) and the pressor response to infusion of AVP were also observed. The results indicate that a G-protein(s) population and/or function may be altered in the vascular smooth muscle of SH rats. This dysfunction may contribute to the heightened pressor responsiveness of the SHR vasculature to SNS and arginine vasopressin (AVP) and the increased sensitivity to the hypotensive effects of nifedipine. NO-synthase activity also appears to be increased in the SHR, suggesting that this increase should reflect a compensatory change due to the elevation of BP in SHR.