Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium

Am J Physiol Heart Circ Physiol. 2014 Jan 15;306(2):H286-90. doi: 10.1152/ajpheart.00733.2013. Epub 2013 Nov 8.

Abstract

In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg(-1)·day(-1)) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.

Keywords: bradykinin; endothelial cells; histamine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Coronary Vessels / injuries
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology
  • Female
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Histamine H1 Antagonists / pharmacology*
  • Histamine H1 Antagonists / therapeutic use
  • Muscle Relaxation / drug effects*
  • Pyrilamine / pharmacology*
  • Pyrilamine / therapeutic use
  • Regeneration*
  • Serotonin / pharmacology
  • Swine
  • Vasodilation
  • Vasodilator Agents / pharmacology

Substances

  • Histamine H1 Antagonists
  • Vasodilator Agents
  • Serotonin
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Pyrilamine
  • Bradykinin