Cardiac adenylate cyclase, cyclic nucleotide phosphodiesterase and lactate dehydrogenase in normotensive and spontaneously hypertensive rats

Abstract

To understand altered physiological responses of hypertrophied spontaneously hypertensive rat (SHR) myocardium to beta-adrenergic receptor stimulation in vivo, myocardial tissues from SHR, normotensive Wistar (NR) and normotensive Wistar-Kyoto (WKY) rats were analyzed for adenylate cyclase, phosphodiesterase and lactic dehydrogenase. While WKY left ventricular adenylate cyclase activity exceeded that of SHR at low (1 and 5 μM) norepinephrine concentrations, there were no further differences. Norepinephrine stimulation of NR and SHR left ventricular adenylate cyclase was the same. In all rat strains similar responses of adenylate cyclase to glucagon were observed. Cyclic AMP phosphodiesterase activity of whole left ventricular homogenates were not significantly different in NR, WKY or SHR when assayed at either 1 mM or μM cyclic AMP. While it was not possible to entirely explain previous hemodynamic findings in vivo on the basis of abnormal cAMP-related enzyme activities, certain other interstrain enzymatic differences were observed. The hypertrophied SHR left ventricle contained higher levels of lactate dehydrogenase (LDH) and an altered isozymic composition as compared to both normotensive strains. These changes may indicate a shift in glycolytic enzyme needs as also seen with artificially produced cardiac hypertrophy. In all rat strains the right ventricular wall has less norepinephrine-stimulatable adenylate cyclase activity and more cyclic AMP phosphodiesterase activity than the left ventricle. These results demonstrate differences in cyclic AMP-related activities between the ventricles and increased LDH activity in the hypertrophied SHR left ventricle.