Prejunctional and postjunctional actions of endogenous norepinephrine at the sympathetic neuroeffector junction in canine coronary arteries

Abstract

The effects of endogenous and of exogenous norepinephrine were studied in isolated rings of canine left circumflex coronary artery and its first ventricular branch. Norepinephrine was released from adrenergic nerve endings by transmural electrical stimulation and by tyramine. In rings contracted with prostaglandin F(2α) transmural electrical stimulation resulted in frequency dependent relaxations which were blocked by propranolol or tetrodotoxin; tyramine and exogenous norepinephrine caused concentration-dependent relaxations which were blocked by propranolol. The tyramine-induced relaxations also were inhibited by cocaine. The left circumflex artery was less sensitive than its branch to β-adrenergic activation; this difference was significant even between rings of the two vessels immediately adjacent to the branching point and was abolished by phentolamine. In the presence of propranolol, transmural electrical stimulation, tyramine and phenylephrine, produced contractions of the left circumflex artery, but not the branch; these contractions were prevented by phentolamine. Phentolamine, but not prazosin, augmented the β-adrenergic response of left circumflex artery to low frequency stimulation; in arteries preincubated with 3H-norepinephrine, this was accompanied by an increased overflow to tritiated neurotransmitter. The prejunctional effect of phentolamine was also evident in branch coronary arteries which exhibit no postjunctional α-adrenergic responses. With high frequency stimulation, both α-adrenergic antagonists equally augmented the relaxation of left circumflex artery; the efflux of tritiated norepinephrine was not different from untreated arteries. These experiments demonstrate, in isolated coronary arteries, that the primary adrenergic response to released endogenous norephinephrine is β-adrenergic relaxation. The prejunctional effect of nonspecific α-adrenergic antagonists preclude their use in determining the importance of postjunctional coronary α-adrenergic receptor activation caused by sympathetic nerve stimulation.