VASODILATOR PEPTIDES - CGRP AND VIP
Authors: Thom S , Hughes A , Martin G , Goldberg P , Server P 
Published: August 2018

The two peptides calcitonin gene related peptide (C6RP) and vasoactive intestinalpeptide (VIP) are widely distributed in animal species including man and a number ofdiverse actions of the peptides have been described [1,2]. They share vasoactive properties [3,4] and may have important functions as neurotransmitters in a non-adrenergic, non-cholinergic nervous system [5]. VIP has been located in perivascular nerves supplying several tissues and is co-stored with acetylcholine in the parasympathetic system [6]. CGRP has also been widely identified in the nervous system, the cardiovascular system and perivascular nerves, where it is located with substance P[7]. Our studies have assessed the activity of these peptides in a human vascular resistance bed -the forearm, and on isolated human blood vessels.

Forearm studies were performed by infusingCGRP (10,30,100 ng/min) or ViP (10,30,100 ng/min) via the brachial artery for 5 min at each dose level and measuring blood flow by venous occlusion plethysmography. In vitro studies were performed using ringsegments of pulmonary, gastric, coronary, radial, and transverse cervical arteries freshly obtained from surgical resection specimens and cerebral arteries obtained from autogsy tissue within 4 hours of death. Vessels were mounted in organ baths containing Krebs buffer aerated with 95% 02, 5% C02 at 37C, and preconstricted using a submaximal concentration of noradrenaline (1-3 μM) or prostaglandin F2a (I-IO11μ7.CGRP or VIP was added to the tissue bath in a cumulative fashion. All arterial segments used for these studies relaxed in response to acetylcholine (0.1-3μM)or A23187 (0.1-3μM) and this was regarded as indicative of functional endothelial integrity. Studies were performed in the presence of indomethacin (lOμM). The endothelium was deliberately removed from some rings and in others haemoglobin (5μM) ormethylene blue (lOμM) were added to the tissue bath after the arterialrings were effectively relaxed by CGRP orVIP. Both peptides produced marked dose dependent increases in forearm blood flow; at 100 ng/min the mean net increase was 174 ± 24% (mean ±s.e.m.) with CGRP, and 223 + 34% (mean +s.e.m.) with VIP. In vitro CGRP (InM-lμM) relaxed preconstricted segments ofradial Tn=2), coronary (n=4), gastric (n=5) and cerebral (n=3) arteries in an endothelium dependent manner. VIP (1 nM - 1pm) also relaxed human gastric (n=2), splenic (n=2), cervical (n=3) and pulmonary (n=5) arteries VIP relaxation of the gastric and cervical arteries was dependent on the presence of endothelium; however, VIP inducedrelaxation of pulmonary artery was not dependent on functional endothelium. The endothelium dependent relaxations could be abolished either by luminal rubbing, additionor haemoglobin or methylene blue.

Together these results might be taken to imply that the forearm vasodilatation response is mediated by EDRF. However, caution is necessary in extrapolating from in vitro observations of large vessels to the in vivo response of a resistance vascular bed.Others have demonstrated that the CGRPand VIP relaxatory responses of smaller human pial arteries (ID 250-600 pm) are endothelium independent [8] and preliminary work in our department supports this. The EDRF mechanism is cyclic GMP linked, but most of the studied functions of VIP and CGRP seem to be linked to a rise in cyclic AMP-. A further paradox is that the blood flow response to infused acetylcholine, the archetypal releaser of EDRF, is evanescent, and yet the vasodilator response to CGRP is persistent.