GUANINE-NUCLEOTIDE REGULATORY PROTEIN ALTERATIONS IN YOUNG MILAN HYPERTENSIVE STRAIN RATS

Vascular smooth muscle cell membranes from prehypertensive rats of the Milan hypertensive strain (MHS) were used to examine adenylyl cyclase activity and its regulation by guanine nucleotide regulatory proteins (G-proteins). Basal adenylyl cyclase activity was similar in MHS and Milan normotensive strain (MNS) membranes. Forskolin (10(-4) M) produced a significantly greater stimulatory response in MHS membranes, but this was not observed with NaF (10(-2) M). Isoproterenol (10(-4) M) caused a significantly decreased stimulation of adenylyl cyclase activity in MHS membranes, while prostaglandin E(1) (10(-5) M) produced similar responses in the two strains. G(i) function and GTP responses, as observed by biphasic effects of GTP on isoproterenol-stimulated membranes, were similar in both strains. The levels of G(i)2 alpha and G(q) alpha/G(11)alpha were similar in the two strains, while the levels of G(s) alpha (44 and 42 kDa forms) and the beta-subunit were significantly reduced by similar to 20% in MHS membranes. The alpha-subunit of G(i)3 was dramatically reduced by similar to 80% in MHS membranes. The affinities of beta-adrenergic receptors for the antagonist, cyanopindolol, were similar in the two strains; however, the number of beta-adrenoceptors was substantially reduced in MHS membranes. These findings may be of relevance to altered vascular reactivity and transmembrane ion distribution observed in the MHS.