GUANINE-NUCLEOTIDE REGULATORY PROTEIN-LEVELS AND FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RAT VASCULAR SMOOTH-MUSCLE CELLS

We compared G-protein levels and function in membranes from vascular smooth-muscle cells (VSMC) derived from mesenteric arteries from SHR, WKY and Wistar rats. Basal adenylyl cyclase activity was significantly reduced in SHR membranes compared with Wistar, but was similar to WKY. Isoproterenol stimulation (10(-4) M) was significantly lower in SHR membranes compared to WKY, but was similar to that in Wistar, which was also significantly lower than WKY. Forskolin (10(-4) M) and NaF (10(-2) M), resulted in a higher stimulatory response in SHR membranes. Biphasic effects of GTP on isoproterenol-stimulated membranes demonstrated unaltered G(i) function in SHR membranes. No significant differences were seen in the levels of G(s)alpha (44- and 42-kDa forms), G(i)2-alpha and the beta-subunit in immunoblotting studies of the membranes. Amounts of G(q)alpha/G11-alpha and G(i)3-alpha were also unchanged. In conclusion, there are differences in adenylyl cyclase responses in SHR VSMC membranes which are not a consequence of altered levels of G-proteins, but may reflect genetic differences rather than effects of hypertension.