ARE CARDIAC G-PROTEINS ALTERED IN RAT MODELS OF HYPERTENSION

Objective: To determine whether alterations in cardiac G-protein number or function, or both, are involved in the desensitization of adenylate cyclase responsiveness in the hypertensive state. Design: Quantitation of G-protein subunits in myocardial membranes from four different rat models of hypertension in comparison with respective normotensive rats. Methods: We compared male and female adult spontaneously hypertensive rats (SHR) with age- and sex-matched Wistar-Kyoto (WKY) rats, rats from the highest-pressure quartile from an F2 generation of WKY x SHR hybrids with those from the lowest-pressure quartile, and one-kidney, one clip renal hypertensive with sham-operated rats. The function of G(salpha) was quantitated by reconstitution of cardiac cholate extracts into cyc- cell membranes with subsequent measurement of NaF-stimulated adenylate cyclase activity. The amounts of immunodetectable G(salpha) G(ialpha) G(qalpha) and G(beta) were determined from quantitative Western blotting experiments with [I-125]-protein A detection. Results: None of the parameters investigated differed significantly between hypertensive and normotensive rats in any of the models investigated. Conclusion: We conclude that major quantitative alterations in cardiac C(S') G(i) or G(q) are not a general feature of the hypertensive state.