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

Abstract

SUMMARY. 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 ¥20, transmural electrical stimulation resulted in frequencydependent 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 /S-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 /?-adrenergic response of left circumflex artery to low frequency stimulation; in arteries preincubated with 3 H-norepinephrine, this was accompanied by an increased overflow of tritiated neurotransmitter. The prejunctional effect of phentolamine was also evident in branch coronary arteries which exhibit no postjunctional a-adrenergic responses. With high frequency stimulation, both a-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 norepinephrine is /S-adrenergic relaxation. The prejunctional effects of nonspecific a-adrenergic antagonists preclude their use in determining the importance of postjunctional coronary a-adrenergic receptor activation caused by sympathetic nerve stimulation. (Circ Res 52: 16-25, 1983)

Regional differences of responses to adrenoceptor agonists in isolated and perfused canine coronary arteries.

“…Miwa and Toda (1984) reported that the maximum contractions induced by KC1 were not different between in large and small coronary arteries of dogs and monkeys. The maximum constrictions produced by PGF2a were greater in large coronary arteries than in small coronary arteries of dogs (Cohen et al 1983 ;Miwa and Toda 1984). Thus, non-adrenergic constrictions induced by KCl and PGF2a were not different between in small and large coronary arteries.…”

“…The same conclusion was reported in the helical strips of canine coronary arteries (Morishita 1979). Phenylephrine did not induce any vasoconstriction in dog and pig small coronary arteries (Bayer et al 1974;Cohen et al 1983). Those results suggested that the small arteries devoided of functioning alpha-adrenoceptors in isolated dog and pig coronary arteries (Bayer et al 1974;Cohen et al 1983).…”

“…Regional variations in reactivities of the human epicardial coronary artery to vasoactive substances were demonstrated in angiographic studies of patients with coronary artery spasm (MacAlpin 1980). The heterogeneous responses of the coronary arteries to vasoactive agents have been reported in vitro (Zuberbuhler and Bohr 1965 ;Bayer et al 1974 ;Morishita 1979;Cohen et al 1983;Miwa and Toda 1984). However, these studies were commonly performed with helical strips and ring preparations in vitro.…”

Influence of Ageing on Vasomotor Responses of Human Epicardial Coronary Arteries

“…Both linear age correlation analysis and comparison of the three different age groups showed significantly stronger contractions to noradrenaline with increasing age of the patients, which was in contrast to the contractions induced by endothelin-1 and the relaxations induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide, which showed no significant age-dependent differences. Noradrenaline, which is released from perivascular sympathetic nerves, mediates vasoconstriction of coronary arteries via a-adrenoceptors and vasodilation via b-adrenoreceptors (Anderson et al 1972;Cohen et al 1983). The main effect of noradrenaline on the coronary artery smooth muscle has often been considered being the a 1 -and a 2 -adrenoceptormediated vasoconstriction (Vatner et al 1970, Holtz et al 1982Heusch et al 1984), whereas other studies have concluded that the b-adrenoreceptor mediated relaxation exceeds the contraction mediated by a-adrenoceptors (Ginsburg et al 1980;Corr & Burnstock 1991).…”

Loss of contractile activity of endothelin‐1 induced by electrical field stimulation‐generated free radicals

“…Moreover, hydroxyl radicals generated by 0.1 mM H202 plus 0.2 mM FeSO4 (Fenton reaction, Freeman & Carpo, 1982) decreased ir-ET-1, and this decrease was significantly inhibited by 10-4 M deferoxamine, a ferrous chelator, and 1200 u ml-' catalase ( Figure 7). ET-1, and PGF2a which is frequently used for the investigation of EFS-induced relaxation of blood vessels (Rooke et al, 1982;Cohen et al, 1983;Feletou & Vanhoutte, 1989). After applying EFS to Krebs-Ringer solution containing each vasoconstrictor (1 tLM AVP, 1 pIm All and 2 !LM PGF2,), the contractile activity of each vasoconstrictor was investigated on porcine coronary artery strips for PGF2, and rat aorta strips for AVP and All.…”