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Eur J Pharmacol ; 667(1-3): 265-70, 2011 Sep 30.
Article in English | MEDLINE | ID: mdl-21640100

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.


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