CARDIAC ADENYLYL-CYCLASE, BETA-ADRENERGIC RECEPTORS, AND G-PROTEINS IN SALT-SENSITIVE HYPERTENSION

The present study investigated whether high salt intake (8%) in Dahl s alt-sensitive and salt-resistant rats with and without hypertension pr oduces a heterologous desensitization of cardiac adenylyl cyclase as o bserved in various types of hypertension and human heart failure. In m embranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, and forskolin-stimulate d adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. Th e activity of the catalyst was depressed, and the expression of the im munodetectable inhibitory G proteins G(ialpha) was increased in Dahl s alt-sensitive rats on 8% sodium chloride, whereas the density of beta- adrenergic receptors and the activity of the stimulatory G protein G(s alpha) reconstituted into G(salpha)-deficient S49 cyc- mouse lymphoma cell membranes were unchanged in any condition studied. We conclude th at high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of G(ialpha) proteins and a depressed catalyst activity of adenylyl c yclase. The results demonstrate that heterologous adenylyl cyclase des ensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in beta-adrenergi c receptors.