We have examined the action of endothelin on healthy and diseased human epicardial coronary arteries to assess its possible role in coronary vascular disorders such as vasospasm and atherosclerosis. Endothelin (10(-10) mol l-1-10(-7) mol l-1) produced dose-dependent contractions in both normal and diseased vessels. The level of constriction was significantly greatly in healthy vessels at 10(-8) mol l-1 endothelin. A greater response was recorded in smaller, more distal vessel segments, irrespective of the pathology of the tissue. Endothelium denudation of disease-free segments had no significant effect on the response to endothelin. In the presence of a threshold dose of endothelin (10(-9) mol l-1), there was no measurable increase in the tension generated by potassium chloride, the thromboxane-mimetic U46619, noradrenaline and histamine. However, the response to 5-HT showed a large increase in arteries from four patients (440-147%) but slight or no increase in arteries from another three patients. We conclude that the interaction with other vasoconstrictor substances is a possible mechanism whereby endothelin may be involved in coronary artery vasospasm. In addition, endothelin may also be involved in the regulation of vascular tone of the small vessels of the heart.

Differences in basal and stimulated cyclic GMP activity in arteries and veins have been shown. This could represent an additional protective mechanism against constrictor influences in arterial bypass grafts, which may explain their documented better long term performance.

Objective-To assess the role of neuropeptides in the control of vascular tone in the human saphenous vein the actions of substance P, vasoactive intestinal peptide, calcitonin gene related peptide, neuropeptide Y, and somatostatin on this blood vessel were examined.Methods-In vitro organ bath techniques were used with preparations of saphenous veins obtained from 29 patients (aged 41-66) who were undergoing coronary bypass surgery.Results-Substance P, vasoactive intestinal peptide, and calcitonin gene related peptide relaxed pre-constricted vessels in a dose dependent manner with a rapid onset of action, taking one to two minutes to reach a plateau at each dose.Substance P (10' to 10' mol/l) induced relaxation with a maximum response (mean (SEM)) 23-0 (6 6)% of the total relaxation induced by glyceryl trinitrate 1 pglml and a 50% maximal effective concentration of 6-8 x 10 molil. Vasoactive intestinal peptide (10`' to 10-moll) produced a relaxation of 27-0 (51)% at 10-' molIl. The maximum responses induced by substance P and vasoactive intestinal peptide were significantly reduced, to 3-7 (2-8)% and 4-7 (2-0)% respectively, after removal of the endothelium. Calcitonin gene related peptide (10"' to 10' mol/1) elicited only 14-3 (2'6)% relaxation at 10' mol/l, and this was not affected by removal The control of vascular smooth muscle tone may partly be mediated by peptidergic mechanisms. Neuropeptides are ubiquitously distributed in human blood vessels,' contributing to vasodilatation (through endothelium dependent or direct action on smooth muscle) and vasoconstriction.23 The endothelium has an important role in controlling vascular tone through the secretion of relaxing and contracting factors derived from the endothelium.' Several peptides induce significant vasomotor effects in human blood vessels through endothelium dependent and endothelium independent mechanisms.378The human saphenous vein is of particular interest as it is the vessel most commonly used for aortocoronary artery bypass grafting.9 Understanding the mechanisms that control vascular tone in this vessel will help the understanding of how the saphenous vein behaves as a bypass graft. We therefore examined the effects of five endogenously occurring peptides on isolated human saphenous veins. MethodsThe study was performed on 111 ring segments taken from 29 patients (aged 41-66) undergoing coronary artery bypass surgery. Human saphenous veins were placed immediately in modified Tyrode's solution composed of 136 8 mM NaCl, 11 9 mM Na HCO3, 2 6 mM KC1, 04 mM NaH2PO4, 2 5 mM MgCl2, 2-5 mM CaCl2, 11 1 mM glucose, and 0 04 mM disodium EDTA. The veins were dissected free of adherent tissues and cut into ring segments 3-5 mm long, which were mounted on two L shaped metal hooks in 5 ml organ baths within one hour. The organ bath solution was maintained at 37°C and gassed continuously with a mixture of 95% oxygen and 5% carbon dioxide. One hook was fixed and the other attached to a force displacement transducer (Grass FTO-3C). The transducer was c...

The purpose of this study was to elucidate the mechanism of action of calcitonin gene-related peptide-induced vasodilatation of human gastroepiploic and internal mammary arteries. Calcitonin gene-related peptide (0.1-100 nmol L-1) elicited relaxations of preconstricted vessels, with a significantly greater effect in the gastroepiploic artery (P < 0.05). This effect was independent of endothelium-derived vasodilating substances. The response of the internal mammary artery but not the gastroepiploic artery to calcitonin gene-related peptide was attenuated by glybenclamide (1.0 mumol L-1) (P < 0.05). In vitro autoradiography indicated that [125I]-calcitonin gene-related peptide bound to the tunica media but not the endothelial cells in both types of artery, with a significantly higher degree of binding in the gastroepiploic artery. It is concluded that calcitonin gene-related peptide acts directly on vascular smooth muscle via specific binding sites to induce vasodilatation. In addition, KATP channels are involved in the action of calcitonin gene-related peptide in the internal mammary artery but not in the gastroepiploic artery.