Vasa nervorum constriction from substance P and calcitonin gene-related peptide antagonists: sensitivity to phentolamine and nimodipine.

Previous work has suggested that vasa nervorum are 'tonically' vasodilated by substance P (SP) and calcitonin gene-related peptide (CGRP) arising from perivascular afferent nerve fibers. Local application of specific receptor antagonists of SP or CGRP results in constriction of vasa nervorum. In this work, we examined the responsiveness of vasa nervorum to epineurial spantide and spantide II (SP antagonists) and hCGRP (8-37) (CGRP antagonist) using serial hydrogen clearance curves in the rat sciatic nerve. Vasoconstriction from spantide and hCGRP (8-37) was dose-dependent, and was slightly greater with spantide than hCGRP (8-37). Spantide II induced vasoconstriction comparable to that of spantide. The vasoconstrictive effects of both spantide and hCGRP (8-37) were eliminated by concurrent systemic treatment with with either phentolamine or nimodipine. The findings support the hypothesis that SP or CGRP blockade interrupts 'tonic' peptide vasodilatation and permits vasoconstriction, perhaps by unopposed adrenergic action mediated through calcium channels. The findings however do not exclude a unique direct vasoconstrictive action of the peptide antagonists.