ENDOTHELIUM-DERIVED RELAXING FACTOR INHIBITION AUGMENTS VASCULAR ANGIOTENSIN-II REACTIVITY IN THE PREGNANT RAT HIND-LIMB

OBJECTIVE: The purpose of our study was to determine whether endothelium-derived relaxing factor plays a role in the blunting of maternal vascular reactivity in pregnancy. STUDY DESIGN: We measured the concentration-pressor responses to norepinephrine (10(-8) to 10(-4) mol/L and angiotensin II (10(-10) to 10(-6) mol/L) in isolated, perfused hind limbs of nonpregnant and pregnant (postmating day 20 to 21) normotensive Wistar-Kyoto and spontaneously hypertensive rats. The hind limbs were perfused at 4 ml/min with Krebs-Ringer solution containing indomethacin (10(-5) mol/L to inhibit prostaglandin production and were either infused with Nomega-monomethyl-L-arginine (10(-4) mol/L), a specific inhibitor of endothelium-derived relaxing factor synthesis, or 0.9% saline solution (untreated). RESULTS: Baseline perfusion pressure was similar in the nonpregnant and pregnant hind limbs of both strains, and Nomega-monomethyl-L-arginine had no effect on perfusion pressure. Norepinephrine induced similar pressor responses in the nonpregnant and pregnant hind limbs of both strains, and Nomega-monomethyl-L-arginine did not alter these responses. Angiotensin II pressor responses were significantly attenuated in the pregnant rat hind limbs compared with the nonpregnant rat hind limbs. Nomega-monomethyl-L-arginine enhanced the angiotensin II responses in the pregnant, but not in the nonpregnant, rat hind limbs. CONCLUSION: The results suggest that rat pregnancy is not associated with generalized refractoriness to all vasoconstrictors and that endothelium-derived relaxing factor plays a role in attenuating vascular reactivity to angiotensin II.