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 (0.1-2 Hz), in atrial myocardial specimens (n=45) from children (n=21) with congenital heart defects, was used to examine the inotropic responses of graded, receptor-selective, endogenous stimulation. Muscle trabeculae subjected to autonomic blockage by timolol, prazosin and atropine showed a slight positive force-frequency relationship (staircase phenomenon). Blockage by atropine/prazosin (i.e. beta-adrenoceptor stimulation) or atropine/timolol (i.e. alpha1-adrenoceptor stimulation) both resulted in positive inotropic effects. A group of specimens opposed by atropine and primarily subjected to frequency variation, secondly was returned to 1 Hz. Stabilization was followed by sequential reversal by beta-blocker (timolol), alpha 1-adrenoceptor stimulation by exogenous noradrenaline, reversal by alpha 1-blocker (prazosin), and finally supramaximal beta-adrenoceptor stimulation (isoprenaline). The maximal levels of inotropic responses mediated by exogenous alpha 1- and beta-adrenoceptor stimulation was estimated. Analysis of the contraction-relaxation cycles revealed that alpha1- and beta-adrenoceptors were recruited differentially. The alpha1-adrenoceptor mediated, endogenous inotropic effect at 1 Hz was close to the level obtained by exogenous noradrenaline stimulation. In contrast, less than 70% of the beta-adrenoceptor mediated, exogenous inotropic effect was expressed by endogenous noradrenaline at the same stimulating frequency, thus indicating that the alpha1-adrenoceptors may be located closer to the adrenergic nerve terminals than the beta-adrenoceptors. There may be a heterogeneous relationship within the same heart as to the relative distance between the nerve terminals and the adrenoceptors. Spatial localization of adrenergic receptors relative to adrenergic nerve terminals adds another aspect to adrenergic regulation. The alpha1-adrenoceptor pathway may play an important role, especially in low-intensity sympathetic inotropic myocardial control, whereas the beta-adrenoceptor pathway adds important effects to the high-intensity sympathetic regulation. Sympathetic activity may thus tonically stimulate the alpha1-adrenoceptor pathway, without necessarily stimulating the beta-adrenoceptor pathway to the same extent.
Borthne
K
K
Institute for Surgical Research, Rikshospitalet, Oslo, Norway.
Langslet
A
A
Lindberg
H
H
Skomedal
T
T
Osnes
J B
JB
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine