Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion

Physiol Genomics. 2003 Apr 16;13(2):169-77. doi: 10.1152/physiolgenomics.00169.2002.

Abstract

Gap-junctional communication coordinates the behavior of individual cells in arterioles. Gap junctions are formed by connexins 40 (Cx40), Cx43, Cx37, and Cx45 in the vasculature. Previously, we have shown that lack of Cx40 impairs conduction of dilatory signals along arterioles. Herein, we examined whether hypertension is present in conscious animals and whether this is a direct effect or due to secondary mechanisms. Mean arterial pressure was elevated by 20-25 mmHg in conscious Cx40-deficient mice (Cx40(-/-)) compared with wild-type controls in both sexes. Differences in heart rate were not observed. Blockade of NO synthase increased pressure equally in both genotypes. Conversely, the angiotensin AT(1)-receptor antagonist, candesartan, decreased pressure to similar extents in Cx40(-/-) and wild-type mice. Acetylcholine and sodium nitroprusside (0.05-15 nmol) were equally potent and effective in decreasing pressure and inducing dilatory responses in the microcirculation. However, in contrast to wild type, Cx40(-/-) arterioles exhibited spontaneous, irregular vasomotion leading temporarily to complete vessel closure. We conclude that loss of Cx40 is associated with hypertension independent of the action of angiotensin II. It is also not related to an altered efficacy of NO or other endothelial dilators. However, the observed irregular vasomotion suggests that peripheral vascular resistance is affected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Angiotensin Receptor Antagonists
  • Animals
  • Arterioles / drug effects
  • Arterioles / enzymology
  • Arterioles / physiopathology*
  • Benzimidazoles / pharmacology
  • Connexins / deficiency*
  • Connexins / genetics*
  • Connexins / physiology
  • Conscious Sedation
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Genotype
  • Heart / drug effects
  • Heart / physiology
  • Hemodynamics / drug effects
  • Hemodynamics / genetics
  • Hemodynamics / physiology
  • Hypertension / enzymology
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microcirculation / drug effects
  • Microcirculation / enzymology
  • Microcirculation / physiopathology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / physiology
  • Organ Size / genetics
  • Tetrazoles / pharmacology
  • Vasodilator Agents / pharmacology
  • Vasomotor System / drug effects
  • Vasomotor System / enzymology
  • Vasomotor System / physiopathology*

Substances

  • Angiotensin Receptor Antagonists
  • Benzimidazoles
  • Connexins
  • Tetrazoles
  • Vasodilator Agents
  • connexin 40
  • Nitric Oxide Synthase
  • Acetylcholine
  • candesartan