Abstract
Objective: This study was undertaken to further elucidate the roles of the vascular endothelium and nitric oxide (NO) in the regulation of vascular tone and constrictor responsiveness in pregnancy.Methods: The perfusion pressure-flow relationship was measured in isolated, perfused, norepinephrine-constricted (1) endothelium-intact, (2) endothelium-denuded, and (3) A-nitro-L-arginine methyl ester (L-NAME)-treated hindlimbs from nonpregnant and term-pregnant rates.Results: Baseline perfusion pressure at a flow rate of 2 mL/min was similar (-20 min Hg) in all hindlimbs. Norepinephrine (0.5 μM) increased perfusion pressure in both nonpregnant (+21.6 ± 2.4 mm Hg) and pregnant (+13.6 ± 0.9 mm Hg) endothelium-intact rat hindlimbs. In nonpregnant rat hindlimbs, endothelium removal and L-NAME increased norepinephrine vasoconstriction similarly (+44.3 ± 4.0 mm Hg and +46.4 ± 8.6 mm Hg, respectively). In pregnant-rat hindlimbs, L-NAME increased norepinephrine vasoconstriction by 43.5 ± 10.8 mm Hg, similar to that in nonpregnant-rat hindlimbs, but endothelium removal only increased norepinephrine vasoconstriction by 28.0 ± 2.2 mm Hg. Perfusion pressure increased linearly as the flow rate was increased from 2 to 4 mL/min, and the slope of the regression line of the endothelium-intact pregnant-rat hindlimbs (7.0 ± 0.6) was slightly, but not significantly, lower than that of the nonpregnant-rat hindlimbs (9.6 ± 0.9). Endothelium removal increased the slopes of the regression lines, but that of pregnant-rat hindlimbs (12.8 ± 1.6) was significantly lower (p ± 0.05) than that of the nonpregnant-rat hindlimbs (23.8 ± 1.8). L-NAME caused a similar increase in the pressure-flow slopes of nonpregnant-rat (36.5 ± 3.4) and pregnant-rat (32.1 ± 5.3) hindlimbs.Conclusions: These results suggest that nonendothelial nitric oxide production may be increased in the hindlimb resistance vasculature of the pregnant rat, which may play a role in the normal pregnancy blunting of constrictor responsiveness and reduction of vascular resistance.
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