Different receptors are involved in the endothelium-mediated relaxation and the smooth muscle contraction of the rabbit pulmonary artery in response to substance P and related neurokinins.

Four neurokinins, substance P (SP), neurokinin A (NKA) neurokinin B (NKB) and kassinin (Kass) were used in the present study together with other peptides and nonpeptide agents to demonstrate the existence of two different neurokinin receptor types in the rabbit isolated pulmonary artery. Similar to other arterial vessels, the endothelium-dependent relaxation of the pulmonary artery in response to neurokinins is due to the activation of a SP-P receptor more sensitive to SP than to the other neurokinins. The endothelium-dependent relaxation is an indirect phenomenon, mediated by an unknown endothelial agent, similar to that released by acetylcholine. The contraction of the pulmonary artery in response to neurokinins is due to receptors of the NK-A type, particularly sensitive to NKA and NKB, and much less sensitive to SP. The contraction is a direct phenomenon, apparently not involving any of the known endogenous autacoids and neurotransmitters or metabolites of arachidonic acid. Contraction appears to be due to stimulation by the neurokinins of receptors located in the arterial smooth muscle. The results presented in this paper indicate that NK-A receptors for neurokinins (which are present in the tracheo-bronchial tree) are also to be found in pulmonary vessels and mediate contraction of arterial vascular smooth muscle, an interesting property of neurokinins.