Cardiac beta-adrenergic signaling pathway alteration in isoproterenol-induced cardiac hypertrophy in male Sprague-Dawley rats.

Abstract

Isoproterenol was continuously administered to rats at a rate of 2.5 microg/kg/min for 7 days via subcutaneously implanted osmotic minipumps. This treatment induced cardiac hypertrophy with increases in heart rate and systolic blood pressure. Beta-adrenoceptor (beta-AR) density decreased in hypertrophied hearts, but the affinity for 125I-cyanopindolol did not change. The beta-AR density decrease did not accompany the change in expression of beta1-AR mRNA. In hypertrophied hearts, adenylyl cyclase activities in the steady state, and stimulated with isoproterenol, forskolin, and manganese, decreased but there was no change in the expression of adenylyl cyclase type V mRNA. The results suggest that beta-AR downregulation and adenylyl cyclase desensitization in isoproterenol-induced cardiac hypertrophy are caused by post-transcriptional changes.