Mechanical stimulation, substance P and vasoactive intestinal polypeptide (VIP) were found to relax the transversal strip of anterior descending branches of pig coronary arteries precontracted by acetylcholine. The effects of mechanical stimulation and substance P required the presence of intact endothelium, while VIP did not. The effect of VIP did not appear to be mediated by catecholamines. Simultaneous measurements of intracellular membrane potential and tension developed by coronary smooth muscle precontracted with Ach showed that the smooth muscle relaxation by substance P is accompanied by membrane hyperpolarization. In contrast VIP relaxed the same tissue without affecting the membrane potential. In a cascade experiment, the fluid perfused intraluminally in intact segments of coronary arteries was dropped over a de-endothelialized strip which relaxed in response to substance P and mechanical stimulation. This indicates that substance P and mechanical stimulation act by releasing from the endothelium a humoral factor that produces arterial smooth muscle relaxation.

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Substance P-immunoreactive nerve fibres were localized by the indirect immunohistochemical method in the adventitia and the adventitial-medial border of large peripheral arteries and veins of the rat. Arteries showed a richer substance P-containing innervation than veins. The superior mesenteric artery was densely innervated, whereas no substance P-containing fibres were found around the carotid artery. Substance P produced a vasoconstriction of the veins, but was basically without effect on arteries, although with the carotid artery a dose-dependent relaxation was observed. The absence of a correlation between the degree of innervation of the blood vessels and their responsiveness to exogenous substance P suggests that there nerves do not subserve a vasomotor function. The depletion of substance P immunoreactivity from nerves in arteries and veins by capsaicin suggest that substance P-containing vascular nerves are primarily sensory in nature.