Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats

Clin Exp Pharmacol Physiol. 2004 May-Jun;31(5-6):302-5. doi: 10.1111/j.1440-1681.2004.03997.x.

Abstract

Chronic heart failure (CHF) impairs endothelium-dependent, nitric oxide (NO)-mediated dilation. This decreased dilation may be partly secondary to the chronic decrease in blood flow, but this hypothesis has not yet been tested. Thus, we assessed whether a localized, chronic increase in blood flow in vivo reverses endothelial dysfunction of small arteries in rats with CHF. Two months after coronary artery ligation or sham surgery, second-order side branches of the superior mesenteric artery were ligated in order to obtain persistently elevated blood flow (HF) in the adjacent first-order side branch compared with normal vessels (NF). One month later, responses to acetylcholine and flow-mediated vasodilatation (FMD) were assessed in vitro in an arteriograph. Chronic heart failure induced a decrease in mesenteric blood flow (374 +/- 25 and 305 +/- 27 micro L/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. Chronic heart failure decreased FMD (maximal response in sham and control 34 +/- 6 and 13 +/- 4%, respectively; P < 0.05). Chronic increases in blood flow did not modify FMD in sham, but restored FMD in CHF rats (28 +/- 4%; P < 0.05 vs CHF NF). The restored response was abolished by an inhibitor of NO synthesis (N(G)-nitro-l-arginine). Chronic heart failure did not affect the abundance of mesenteric endothelial NO synthase (eNOS) mRNA. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non-significantly in CHF rats. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Heart Failure / physiopathology*
  • Rats
  • Splanchnic Circulation / physiology*
  • Vascular Diseases / physiopathology
  • Vasodilation / drug effects
  • Vasodilation / physiology*

Substances

  • Acetylcholine