Vasorelaxation in isolated bone arteries: Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide bradykinin studied in pigs

Abstract

We assessed the effects of vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and bradykinin in arteries (diameter = 230 μm) isolated from cancellous bone from pigs. Arterial segments (2 mm long) were mounted on a myograph for measurement of isometric force development. After submaximal pre-contraction with norepinephrine, VIP (10−10-10−7 M), CGRP (10−11-10−7 M), SP (10−6 M), and bradykinin (10−11-10−6 M) were added. 44 arterial segments (23 pigs) were investigated. VIP-, CGRP-, and bradykinin induced a concentration-dependent vasorelaxation, while SP mediated a transient relaxation. After mechanical removal of the endothelium, the effects of SP and bradykinin were completely abolished, while the relaxation to CGRP was still pronounced. This indicates that the effects of SP and bradykinin are mediated by the endothelium, while CGRP mainly mediates relaxation by a direct effect on vascular smooth muscle cells. The relaxations to CGRP and bradykinin were still significant after inhibition of nitric oxide synthase with 10−4 M N -nitro-L-arginine (L-NNA) and inhibition of prostaglandin synthesis with 10−5 M indomethacin, indicating the existence of an alternative vasorelaxing pathway. Our findings support the theory of a vaso-regulatory role of neuropeptides in bone.