DOCA-SALT HYPERTENSIVE RAT HEARTS EXHIBIT ALTERED EXPRESSION OF G-PROTEINS

We have recently demonstrated an alteration in the levels of G-proteins and their correlation with adenylyl cyclase in spontaneously hypertensive rats (SHR). In the present studies we examined if the other models of hypertensive rats, such as DOCA-salt hypertensive rats (HR), also exhibit the similar alterations in G-protein and in adenylyl cyclase activity. We have determined the adenylyl cyclase activity stimulated and inhibited by hormones, as well as the levels of G-proteins using specific antibodies and cDNA probes in the hearts from DOCA-salt HR and their sham-operated controls after 2 and 4 weeks of treatment. Adenylyl cyclase activity stimulated by GTPgammaS, isoproterenol, and glucagon was significantly decreased in heart sarcolemma from DOCA-salt HR as compared to their controls after 2 and 4 weeks of treatment. In addition, the inhibitory hormones inhibited the enzyme activity to a greater extent in hypertensive rats than controls. Furthermore, the levels of G(ialpha-2) and G(ialpha-2) mRNA, as determined by immunoblotting and Northern blotting techniques, respectively, were higher in hearts from DOCA-salt HR. However, the levels of G(salpha45) were decreased in these rats. These results indicate that, similar to SHR, the hearts from DOCA-salt HR exhibit the increased expression of G(i), however unlike SHR, the expression of G(s) was decreased. It is suggested that the altered expression of G-proteins may partly be responsible for the decreased responsiveness of adenylyl cyclase to hormone stimulation and increased responsiveness to hormone inhibition in DOCA-salt hypertension.