Differential recruitment of alpha(1)- and beta-adrenoceptors in inotropic control of atrial child myocardium by endogenous noradrenaline

Noradrenaline release, graded by frequency Variation of field stimulation 1 0.1-2 Hz), in atrial myocardial specimens (n = 45) from children (n = 21) w ith congenital heart defects, was used to examine the inotropic responses o f graded, receptor-selective, endogenous stimulation Muscle trabeculae subj ected to autonomic blockage by timolol, prazosin and atropine showed a slig ht positive force-frequency relationship (staircase phenomenon). Blockage b y atropine/prazosin (i.e. beta-adrenoceptor stimulation) or atropine/timolo l (i.e, alpha(1)-adrenoceptor stimulation) both resulted in positive inotro pic effects. A group of specimens opposed by atropine and primarily subject ed to frequency variation, secondly was returned to 1 Hz. Stabilization was followed by sequential reversal by beta-blocker (timolol), alpha(1)-adreno ceptor stimulation by exogenous noradrenaline, reversal by alpha(1)-blocker (prazosin), and finally supramaximal beta-adrenoceptor stimulation (isopre naline). The maximal revels of inotropic responses mediated by exogenous al pha(1)- and beta-adrenoceptor stimulation was estimated. Analysis of the co ntraction-relaxation cycles revealed that alpha(1)- and beta-adrenoceptors were recruited differentially. The alpha(1)-adrenoceptor mediated, endogeno us inotropic effect at 1 Hz was close to the level obtained by exogenous no radrenaline stimulation. In contrast, less than 70% of the beta-adrenocepto r mediated, exogenous inotropic effect was expressed by endogenous noradren aline at the same stimulating frequency, thus indicating that the alpha(1)- adrenoceptors may be located closer to the adrenergic nerve terminate than the beta-adrenoceptors. There may be a heterogenous relationship within the same heart as to the relative distance between the nerve terminals and the adrenoceptors. Spatial localization of adrenergic receptors relative to ad renergic nerve terminals adds another aspect to adrenergic regulation. The alpha(1)-adrenoceptor pathway may play an important role, especially in low -intensity sympathetic inotropic myocardial central, whereas the beta-adren oceptor pathway adds important effects to the high-intensity sympathetic re gulation. Sympathetic activity may thus tonically stimulate the alpha(1)-ad renoceptor pathway, without necessarily stimulating the beta-adrenoceptor p athway to the same extent.