Cholinergic constriction in the general circulation and its role in coronary artery spasm.

Abstract

The release of acetylchoUne from autonomic nerves in those tissues that receive a cholinergic innervation is widely believed to dilate blood vessels. Exogenously administered acetylchoUne hi vivo does dilate vascular beds and produce hypotension; however, this latter effect is indirect and probably the result of liberation of endothelium-derived relaxing factor (EDRF) from endothelial cells. Some blood vessels contain a substantial population of medial constrictor receptors for acetylchoUne, and the implications of this presence for vascular control systems has been largely ignored, although it needs to be considered. A survey of the evolution of vasomotor control systems indicates that acetylchoUne serves principally as an excitatory transmitter to blood vessels. NeuraUy mediated cholinergic constriction and not dilation is found in fish, amphibians, reptiles, and birds, with responses initiated by medial muscarinic receptors. AcetylchoUne constricts many vascular preparations from these lower animals, but some vessels relax, reflecting the emergence of an EDRF responsive to acetylchoUne. An examination of cholinergic responses in mammalian vessels reveals that cholinergic (neurogenic) dilation is limited to a very few vascular beds and to only a few species. Both experimental evidence and evolutionary considerations support the likelihood that cholinergic (neural) constriction operates in some vascular regions in mammals and, in particular, in the coronary circulation of some species, including humans. In fact, constriction, and not dilation, may be the dominant vascular response to activation of the cholinergic axis in most mammals, including humans. The complications and contradictions introduced by the simultaneous presence of both EDRF and a cholinergic constrictor innervation involving medial muscarinic receptors are discussed. A variety of evidence is also presented that implicates cholinergic constriction in at least some instances of coronary artery spasm and sudden death. Received March 3, 1988; accepted January 24, 1989. little to say about neurogenic acetylcholine, except to reiterate its traditional functional assignment to a few specialized vascular beds, such as the male genitalia, the nasal mucosa, and the submandibular salivary glands. 3 -s Even such specific attributions of function, however, have generated little research interest in cholinergic mechanisms per se but instead have focused attention on the role of vasoactive peptides in neurogenic dilation. 6In fact, vasodilation by endogenously liberated acetylcholine, in those few beds in which it is postulated to occur, is linked to such ambiguities and uncertainties, with hardly a single exception, as to suggest that even such a restricted and modest assignment may overstate its role. As will be discussed here, the purported cholinergic vasodilator innervation of skeletal muscle, 7 -9 presumed to be activated as part of the defense reaction in the cat and dog, is unverifiable in primates, 10 and its hypothesized role in dilation of thoro...

Acetylcholine-Induced Coronary Vasoconstriction and Negative Inotropy in the Neonatal Pig Heart

“…This vasoconstriction was abolished by atropine, and thus is muscarinic receptor mediated. In support of our findings, recent studies have shown that ACh contracts large coronary arteries isolated from adult pigs (5) and humans (6). The mechanism by which ACh causes this vasoconstriction , however, has not been delineated.…”

“…Our hearts were perfused at constant coronary flow, and thus it is unlikely that vasoconstriction impaired myocardial oxygen delivery. Nevertheless, coronary vasoconstriction to ACh may be heterogenous (6,21), e.g. in regard to responses in epicardial versus endocardial vessels.…”

“…ACh has also been shown to relax precontracted, epicardial coro nary arteries isolated from several species, mo st notably the dog (4). It has becom e apparent, however, that the se results cannot be generalized to all mammals, because large coronary art eries of adult pigs (5) and humans (6,7) can constrict in vitro to exogeno usly adm inistered ACh. Recently, Cowa n and McKenzie (8) demonstrated that ACh reduces myocardial blood flow when injected into the left ant erior descend ing coronary artery of in vivo adult pig hearts .…”

ST-segment Elevation of Electrocardiogram in a Patient with Shoshin Beriberi

“…Wilde et al (21) mentioned that thiamine deficiency can lead to ST-segment elevation in the right precordial leads. Previous studies have demonstrated that various central and autonomic nervous system abnormalities can result in ST-segment elevation with or without CK elevation (22)(23)(24)(25)(26)(27). The autonomic nervous function also participates in the formation of Brugadatype ECG (28,29), and unbalanced autonomic nerve function has been thought to play an important role in inducing Brugada-type ECG (30).…”

Altered reactivity of pulmonary vessels in postobstructive pulmonary vasculopathy

“…Contraction has also been reported in the pulmonary vessels of rabbits (Altiere et al, 1986) and in coronary arteries of most species (Kalsner, 1989), with thromboxane A 2 being the putative Mediator since constriction could he prevented by cyclooxygenase inhibitors, thromboxane A 2 synthase inhibitors and thromboxane A 2 antagonists (Altiere ., 1986). In addition, our findings seem to exclude an important role for prostaeyclin, another endothelium-derived relaxing factor, in the ACh-induced relaxation of guinea pig pulmonary arteries.…”