Reduced cAMP levels and glycogen phosphorylase activation in isoproterenol perfused SHR myocardium.

Abstract

The effect of isoproterenol perfusion on cAMP levels and phosphorylase activity was investigated in the spontaneously hypertensive rat (SHR) and Kyoto Wistar normotensive control rat (WKY) heart. The basal force of contraction in physiological salt solution perfused hearts was comparable between SHR and WKY. However, the force of contraction in response to 10 nM isoproterenol perfusion was decreased approximately 20-30% in SHR heart as compared to WKY heart. Basal cAMP levels were reduced in SHR hearts as compared to WKY hearts. Isoproterenol perfusion resulted in an increase in cAMP levels over the basal cAMP values which was 50% and 100% in SHR and WKY hearts, respectively. Basal phosphorylase activity was higher in SHR hearts as compared to WKY hearts. However, the percentage increase in phosphorylase activity by isoproterenol perfusion over the basal values was approximately 400% in WKY hearts and only 200% in SHR hearts. The ouabain-sensitive (Na+, K+)-ATPase activity, Ca2+ binding in the absence of ATP, sialic acid content, and 5'-nucleotidase activity of purified cardiac plasma membranes was not altered in SHR as compared to WKY. These results would suggest beta-adrenergic mediated adenylate cyclase stimulation is decreased in SHR myocardium while other plasma membrane properties and associated enzymes may not be altered.