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

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.