Guanine nucleotide regulatory protein alterations in young Milan hypertensive strain rats

Abstract

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 normontensive strain (MNS) membranes. Forsokolin (10 −4 M) produced a significantly greater stimulatory response in MHS membranes, but this was not observed with NaF (10 −2 M). Isoporterenol (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 i2α and G qα/G 11α were similar in the two strains, while the levels of G sα (44 and 42 kDa forms) and the β-subunit were significantly reduced by ∼20% in MHS membranes. The α-subunit of G i3 was dramatically reduced by ∼80% in MHS membranes. The affinities of β-adrenergic receptors for the antagonist, cyanophindolol, were similar in the two strains; however, the number of β-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.