Endogenous modulation of the blunted adrenergic response in resistance-sized mesenteric arteries from the pregnant rat.

Abstract

We tested the hypothesis that during pregnancy the endothelium mediates the blunted response to adrenergic vasoconstriction. Mesenteric resistance arteries from late pregnant (n = 6) and age-matched virgin control (n = 6) Sprague-Dawley rats were studied in a myograph. Arteries from pregnant rats were 35% less sensitive to phenylephrine vasoconstriction than were those from nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.48 mumol/L, pregnant vs nonpregnant, p < 0.01). Meclofenamate had no effect on the vasoconstrictor response in arteries from either group. Inhibition of endothelium-derived relaxing factor with N(o)-nitro-L-arginine methyl ester or endothelial cell removal had a similar twofold increase in phenylephrine sensitivity in arteries from both the pregnant and nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.11 mumol/L for pregnant rats and 1.48 vs 0.72 mumol/L for nonpregnant rats, p < 0.01). However, methacholine relaxation response was potentiated in pregnant versus nonpregnant rats (mean effective concentration that produced a 50% response 0.030 vs 0.049 mumol/L, p < 0.01). Although the potential for endothelium-dependent relaxation is augmented in mesenteric arteries of the pregnant rat, the decreased sensitivity to phenylephrine during pregnancy is not modulated acutely by endothelium-derived relaxing factor or by prostaglandin products of the cyclooxygenase pathway.