Actions of constrictor (NPY and endothelin) and dilator (substance P, CGRP and VIP) peptides on pig splenic and human skeletal muscle arteries: involvement of the endothelium

Abstract

1. The effects of various vasoactive peptides and the involvement of the endothelium in these effects were studied on small human skeletal muscle arteries (SMA) and pig splenic arteries (SA) in vitro. 2. Under control conditions, neuropeptide Y (NPY) caused potent and strong contractions of both arteries. The maximal effect of NPY 500 nM was similar to that of phenylephrine and noradrenaline (10 microns). Endothelin was approximately 10 fold more potent than NPY in contracting SA, and the maximal response to endothelin 50 nM was 130% of that evoked by phenylephrine. 3. After removal of the endothelium (by rubbing the inner surface of the arteries) neither the maximal effect nor the EC50 value of NPY on SMA and SA or those of endothelin on SA were changed from control conditions. 4. The substance P (SP)-induced relaxation of precontracted SMA and SA during control conditions (80-90%) was abolished or greatly reduced after endothelium removal. 5. Under control conditions, calcitonin gene-related peptide (CGRP) was about 10 times more potent than vasoactive intestinal polypeptide (VIP) in relaxing SMA. After endothelium removal the relaxation induced by CGRP on SMA and SA and that of VIP on SMA were not changed from control conditions. 6. It is concluded that, in the SMA and SA, the potent vasoconstrictor effects of NPY and endothelin are mediated by direct actions on the vascular smooth muscle and not via a release of an endothelium-derived contracting factor. Relaxation induced by SP but not that of CGRP and VIP seems to be mediated via the endothelium.