Reduction in the activity of the stimulatory guanine nucleotide-binding protein in the myocardium of spontaneously hypertensive rats

Abstract

The beta-adrenergic receptor-adenylate cyclase system of the cardiac membranes in spontaneously hypertensive rats (SHR) 14 weeks old was studied. The maximal activity of the catalytic unit of adenylate cyclase stimulated by purified stimulatory guanine nucleotide-binding protein (Ns) or forskolin was higher in SHR than in control Wistar-Kyoto (WKY) rats. However, adenylate cyclase activity stimulated by isoproterenol and GTP was the same between SHR and WKY rats. Although there was no difference in the amount of Ns which was measured by cholera toxin-catalyzed ADP-ribosylation, the functional activity of Ns in cholate-extracted membranes from SHR was significantly lower than that from WKY rats. There were no strain differences in the number and affinity of beta-adrenergic receptors; the function and amount of the inhibitory guanine nucleotide-binding protein (Ni), and the amount of beta gamma-subunits of Ns and Ni. These findings showed that there is an abnormal signal transduction in this system in SHR due to a reduction in the functional activity of alpha-subunits of Ns.