title: End o' the line revisited: moving on from nitric oxide to CGRP.
abstract: When endothelin-1(ET-1) was discovered it was hailed as the prototypical endothelium-derived contracting factor (EDCF). However, over the years little evidence emerged convincingly demonstrating that the peptide actually contributes to moment-to-moment changes in vascular tone elicited by endothelial cells. This has been attributed to the profound inhibitory effect of nitric oxide (NO) on both the production (by the endothelium) and the action (on vascular smooth muscle) of ET-1. Hence, the peptide is likely to initiate acute changes in vascular diameter only under extreme conditions of endothelial dysfunction when the NO bioavailability is considerably reduced if not absent. The present essay discusses whether or not this concept should be revised, in particular in view of the potent inhibitory effect exerted by calcitonin gene related peptide (CGRP) released from sensorimotor nerves on vasoconstrictor responses to ET-1.
authors.affiliation: Institute of Molecular Medicine, University of South Denmark, Odense, Denmark; Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.affiliation: Institute of Molecular Medicine, University of South Denmark, Odense, Denmark; Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China. Electronic address: vanhoutt@hku.hk.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D014666:Vasomotor System / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide
keywords: Arterial blood pressure; Calcitonin gene related peptide; ET(A) receptors; ET(B) receptors; Endothelin-1; Endothelium; Exocytosis; Nitric oxide; Nitric oxide synthase; Oxidative stress; Vascular tone