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Effects of aging and hypertension on the participation of endothelium-derived constricting factor (EDCF) in norepinephrine-induced contraction of rat femoral artery

Eur J Pharmacol. 2011 Sep 30;667(1-3):265-70. doi: 10.1016/j.ejphar.2011.05.031. Epub 2011 May 27.

Abstract

Endothelium-dependent contraction elicited by high concentrations of acetylcholine was described in hypertensive as well as in aged normotensive rats. The contribution of endothelium-derived constricting factor (EDCF) to norepinephrine-induced contraction is still unknown. We aimed to compare EDCF participation to norepinephrine-induced arterial contraction in spontaneously hypertensive rats (SHR) and aged normotensive Wistar-Kyoto (WKY) rats. Femoral arteries from either adult (7-months-old) or aged (14-months-old) animals were placed in myograph and norepinephrine-induced concentration-response curves were recorded under control conditions and in the presence of indomethacin (cyclooxygenase inhibitor, 10(-5) mol/l) or L-NNA (NO synthase inhibitor, 10(-4) mol/l) or both. Norepinephrine-induced concentration-response curve was enhanced in SHR compared to WKY rats, but concentration-response curve of aged WKY rats was similar to those of adult SHR. Cyclooxygenase inhibition largely attenuated concentration-response curves in all groups. However, this effect was greater in aged WKY rats and adult SHR compared to adult WKY rats. NO synthase inhibition augmented norepinephrine-induced contraction in arteries of adult WKY rats, but not in arteries from aged WKY rats or adult SHR. The combined administration of L-NNA and indomethacin had no additive effects on concentration-response curves. EDCF contribution to norepinephrine-induced contractions of arteries was considerably greater in adult SHR (80±3%) and aged WKY rats (86±2%) compared to adult WKY rats (35±10%). The inhibition of NO synthase augmented EDCF contribution to norepinephrine-induced contraction only in arteries from adult WKY rats (76±9%). We conclude that EDCF contribution to norepinephrine-induced contraction of conduit arteries is similarly enhanced in adult hypertensive and aged normotensive rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelins / metabolism*
  • Femoral Artery / drug effects*
  • Femoral Artery / metabolism
  • Femoral Artery / physiology*
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Norepinephrine / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Vasoconstriction / drug effects*

Substances

  • Cyclooxygenase Inhibitors
  • Endothelins
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases
  • Acetylcholine
  • Norepinephrine
  • Indomethacin