Coronary arteries from hearts of cardiac patients contain significantly higher concentrations of histamine than do those from noncardiac patients. The coronary vessels of cardiac patients are also hyperresponsive to histamine and serotonin. These differences between groups of patients suggest an explanation for coronary artery spasm in heart disease.

Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing effects of hydrocortisone without materially interfering with potentiation produced by cocaine which is mediated through an independent mechanism unrelated to amine inactivation. Hydrocortisone also abolished the enhancing effects of known COMT inhibitors. It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines. Others have observed that responses of the conjunctival vascular bed of rabbits and man to norepinephrine were potentiated 15 minutes after local application of hydrocortisone or cortisone (3,4).Several reports indicate that hydrocortisone potentiates the pressor effects of epinephrine but not that of norepinephrine in the cat, rabbit, and dog (5, 6). In agreement with these findings, Kadowitz and Yard (7) observed that the blood vessels of the denervated and pump-perfused hindquarters of cats show an increased constriction in response to epinephrine but not to norepinephrine after hydrocortisone. However, in-vitro preparations of arterial smooth muscle show increased responsiveness to both epinephrine and norepinephrine within several minutes after exposure to hydrocortisone (6,8,9).

Hydrocortisone potentiates responses to adrenaline and noradrenaline in aortic strips by inhibiting their inactivation by catechol-O-methyl transferase (Kalsner, 1969). It was of interest to determine whether other steroid hormones also enhance responses to catecholamines and decrease their rate of inactivation by 0-methylation. In the present study the effects of 17f-oestradiol, progesterone and desoxycorticosterone on responses to a variety of sympathomimetic amines were investigated. MethodsRabbit aortic strips, prepared according to Furchgott (1960), were suspended under 2 g tension in 15 ml. chamibers containing Krebs-Henseleit (Krebs) solution

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...