The beta-
adrenoceptor adenylate cyclase complex (beta ACR), located in the sarcolemmal membrane, is one of the most effective signal transduction systems regulating function and metabolism of heart muscle primarily via
cyclic AMP. It is thought to play an important role in adaptive mechanisms of the heart as to pressure load and stressful stimuli. Present knowledge about composition and function of beta
ARC enable us to clear up which of the single components of this system contributes to pathophysiological alterations of heart function. Cardiac beta
ARC was investigated in three experimental groups: I) adult rats of WKY strain (WKY), II) adult rats of WKY strain
cardiac hypertrophy in which was induced by aortic constriction (WKYAC), and III) adult spontaneously hypertensive rats (SHR). Quantitative assessment of beta-
adrenoceptor number (beta AR) as revealed by [3H]
dihydroalprenolol binding studies showed a significant reduction to 30% and 35% of control beta AR in membrane preparations of WKYAC and SHR, respectively. The diminished density of myocardial beta AR was accompanied by a reduction of the maximum stimulatory effect of 1(-)
adrenaline on
adenylate cyclase (AC). Evidence was obtained for a close correlation between the diminished response of beta
ARC to beta AR-mediated stimuli and the heart index as measure of
cardiac hypertrophy. No correlation between graduated states of
hypertrophy and activation of AC has been observed by NaF and
Gpp(NH)p. The results indicate that in rat hearts severe
hypertrophy of which was induced by pressure-load, mainly the beta AR component of the beta
ARC complex contributes to the reduction of beta
ARC-mediated responsiveness of the hypertrophied myocardium.