Age-dependent changes in the myocardial adenylate cyclase of normotensive and spontaneously hypertensive rat

The activity of myocardial adenylate cyclase from two age groups (10-11 and 18-19 weeks old, respectively) of male spontaneously hypertensive rats (SHR) and their age-matched normotensive Wistar-Kyoto rats (WKY) was examined. Stimulation of the enzyme by isoproterenol and 5'-guanylyl-imidodiphosphate (GMP-PNP) was decreased for both SHR and WKY at the older age. In addition, decreased sensitivity of the enzyme to NaF was also found for older SHR. Except for showing subsensitivity to isoproterenol, the enzyme from SHR at 10-11 weeks of age was activated by GMP-PNP alone, or in combination with isoproterenol, and NaF to the same extent as that from the same age group of WKY. Stimulation of the enzyme by these activators was considerably lower from SHR than from WKY at 18-19 weeks of age. These data indicate that myocardial adenylate cyclase from SHR initially demonstrates a selective decrease in response to isoproterenol, and then a generalized decrease in sensitivity to various activators at a later hypertensive stage.