Signal transfer in cardiac muscle. Alteration of the beta-adrenoceptor adenylate cyclase system in the hypertrophied myocardium.
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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases