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Effect of Indomethacin and N-Nitro-L-Arginine Methyl Ester on the Pressure/Flow Relation in Isolated Perfused Hindlimbs From Pregnant and Nonpregnant Rats

Division of Maternal/Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee; Departments of Obstetrics and Gynecology and Physiology/Biophysics, University of Tennessee Memphis, 800 Madison Avenue, Memphis, TN 38163

Steven A. Friedman, MD

Baha M. Sibai, MD

Division of Maternal/Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee

Objective: To compare the pressure/flow relationship and to assess the roles of prostaglandins and nitric oxide in flow-induced vasodilation in the nonpregnant and late-pregnant rat hindlimb vasculture.

Methods: Pressure/flow and conductance/flow relationships were determined in isolated, Krebs buffer-perfused, norepinephrine (0.5 µmol/L) preconstricted hindlimbs from nonpregnant and late-pregnant Wistar-Kyoto rats before and after inhibition of cyclo-oxygenase with indomethacin (20 µmol/L), or nitric oxide synthase with N-nitr-L-arginine methyl ester (300 µmol/L).

Results: There were no significant differences in baseline perfusion pressure between nonpregnant and pregnant rat hindlimbs perfused at 2 mL/min (20.6 ± 0.8 and 19.7 ± 1.1 mmHg, respectively) and nonepinephrine increased perfusion pressure about twofold (40.8 ± 2.0 and 34.8 ± 1.8 mmHg, respectively). After constriction, perfusion pressure increased linearly as flow was increased in a stepwise manner to a maximum of 4 mL/min. The slope of the pressure/flow regression line for the pregnant rat hindlimbs (6.00) was significantly lower (P 001) than that for the nonpregnant rat hindlimbs (8.44). Vascular conductance also increased as flow was increased, and was significantly greater at all flow rates in the pregnant compared to the nonpregnant rat hindlimbs. Indomethacin slightly decreased the constrictor response to norepinephrine and increased the pressure/flow regression line slope in nonpregnant, but not in pregnant rat hindlimbs. N-nitro-L-arginine methyl ester abolished flow-mediated vasodilation in nonpregnant and pregnant rat hindlimbs, and there was no longer any significant difference between the pressure/flow regression line slopes.

Conclusion: These results suggest that flow-induced vasodilation, mediated by endothelium-derived nitric oxide, is enhanced during pregnancy allowing the maternal vasculature to accommodate increased blood flow without increased blood pressure.

Key Words: Pregnancy • vascular conductance • nitric oxide • prostaglandin • perfused hindlimb

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