Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1

Br J Pharmacol. 2002 Aug;136(8):1146-52. doi: 10.1038/sj.bjp.0704815.


1 The potential vasodilator function of the peptide ghrelin, recently identified as the endogenous ligand of the growth hormone secretagogue orphan receptor (GHS-R), was investigated in human endothelium-denuded internal mammary artery. The peptide endothelin-1 (ET-1) is a potent and long-lasting vasoconstrictor. Comparisons were made with established and putative endogenous vasodilators to determine if any could reverse ET-1-induced vasoconstriction in this vessel. 2 Ghrelin (0.1-300 nM) potently dilated 10 nM ET-1-induced constrictions (pD(2) 8.39+/-0.29; E(MAX) 63+/-5.6%; n=9/14, responders/total). 3 ANP (pD(2) 7.75+/-0.14; E(MAX) 106+/-2.0; n=5/5) and CGRP (pD(2) 8.08+/-0.17; E(MAX) 76+/-15% n=5/6) both produced complete reversal of the constrictor response to ET-1 (E(MAX) not significantly different from 100%, P>0.05 one-sample t-test). 4 The following caused partial reversal of the ET-1 response: Adrenomedullin (n=9/9) and two peptides derived from proadrenomedullin, PAMP-12 (n=6/7) and PAMP-20 (n=9/9) (pD(2) values 7.63+/-0.28, 7.97+/-0.23 and 8.51+/-0.29; E(MAX) 58+/-7.3, 54+/-10 and 51+/-7.8% respectively). Unexpectedly, amylin was only 2 fold less potent than CGRP, although there was less than 50% reversal of the ET-1 constriction (pD(2) 7.86+/-0.30; E(MAX) 41+/-5.4%; n=7/9). CNP (n=6/6) also partially reversed constrictions to ET-1 (E(MAX) 53+/-6.3; pD(2) 8.07+/-0.38). 5 BNP (n=4/5) and PGI(2) (n=6/8) were weak vasodilators, since concentration-response curves failed to reach a maximum within the range tested. PGE(2) caused a small dilatation in some vessels (E(MAX) 17+/-2.1%; pD(2) 8.63+/-0.36; n=4/8). 6 We have demonstrated ghrelin to be an effective, endothelium-independent vasodilator of the long-lasting constrictor ET-1 in human arteries producing responses similar to those of adrenomedullin (P>0.05, ANOVA). British Journal of Pharmacology (2002) 136, 1146-1152

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Endothelin-1 / antagonists & inhibitors*
  • Female
  • Ghrelin
  • Humans
  • In Vitro Techniques
  • Male
  • Mammary Arteries / drug effects*
  • Mammary Arteries / physiology
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Peptide Hormones / pharmacology
  • Peptide Hormones / physiology*
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology


  • Endothelin-1
  • Ghrelin
  • Peptide Hormones
  • Vasodilator Agents