Vascular actions of airway neuropeptides

We have studied effects of several neuropeptides perfusing the cranial tracheal arteries bilaterally in anesthetized dogs. All the neuropeptides tested produced dose-related changes in vascular resistance. Substance P and VIP had similar potencies in decreasing tracheal vascular resistance. Neurokinin A (NKA) was the most potent dilator. Calcitonin gene-related peptide (CGRP) and peptide histidine isoleucine (PHI) were about 10 and 100 times less potent than NKA, respectively. Neuropeptide tyrosine (NPY) was one of the few constrictors of tracheal vessels at doses above 10(-11) mol. There seemed to be major differences between the neuropeptides with regard to the onset and duration of their vascular effects. NKA and PHI usually caused maximal vasodilatation within 15 to 30 s after the injection into the tracheal artery, and their vascular responses subsided within 1 to 2 min. With CGRP, the maximal dilatation of tracheal vessels came somewhat later, and more than half of the vascular response was still present 10 min after the injection of this neuropeptide. The maximal vasoconstrictor response to NPY came slowly, and the constriction showed only a little tendency to subside within 10 min after the injection. These results indicate that the long-acting neuropeptides VIP, CGRP, and NPY may be more important than the short-acting NKA and PHI in the physiologic regulation of airway blood flow. All the neuropeptides studied had effects on the contralateral tracheal vascular resistance. They were much more powerful than the classic mediators histamine and methacholine.