INTRAMURAL NERVE-MEDIATED INOTROPIC RESPONSES OF LEFT ATRIA OF RATS AND GUINEA-PIGS - DEMONSTRATION OF ALPHA-ADRENERGIC AND NONADRENERGIC NONCHOLINERGIC RESPONSES IN GUINEA-PIGS

  • 1 November 1987
    • journal article
    • research article
    • Vol. 243  (2) , 723-730
Abstract
The effects of transmural nerve stimulation (TNS) on contractile responses of rat and guinea pig atria were analyzed pharmacologically. Isolated left atria were electrically driven through AgAgCl field electrodes and TNS was performed by brief introduction of defined stimulation patterns through the same electrodes. Step elevations in stimulating voltage induced biphasic inotropic responses in the left atria of both species: an initial negative component which was usually overwhelmed by a subsequent positive one. The transient negative inotropic response was induced by parasympathetic cholinergic nerve excitation, inasmuch as it was abolished by atropine. In the left atrium of the rat, the TNS-induced positive inotropic response was due exclusively to adrenergic nerve excitation through activation of beta-1 adrenoceptors. In contrast, analysis of the time course of responses in guinea pig left atria after nerve stimulation at 10 Hz revealed a positive inotropic response consisting of two phases; rapid and delayed phases were superimposed upon each other. The rapid phase was reduced by atenolol, a beta-1 antagonist, and attenuated further by prazosin, an alpha-1 antagonist. In the presence of both atenolol and prazosin, TNS of guinea pig left atria still induced a positive inotropic responses but it had a slow onset and decay. This is termed the delayed phase response. TNS induced a similar delayed inotropic response in atria from surgically sympathectomized or reserpine-pretreated guinea pigs, from which catecholamine-fluorescence nerves and responses to tyramine were absent. These results demonstrate that TNS excitated adrenergic, cholinergic and nonadrenergic noncholinergic nerves in guinea pig left atria. The rapid phase of the TNS-induced positive inotropic response was mediated by neuronally released norepinephrine through activation of not only beta-1 but also alpha-1 adrenoceptors, and the delayed phase was mediated by nonadrenergic noncholinergic nerves.