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Endothelium-derived relaxing factor inhibition and the pressor response to norepinephrine in the pregnant rat
1Department of Obstetrics and Gynecology, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Objective:
To determine whether endothelium-derived relaxing factor (EDRF) plays a role in the blunted pressor response to norepinephrine that is characteristic of normal pregnancy.
Methods:
Eleven pregnant (mean +/- standard error of the mean 18 +/- 1 days of gestation) and 11 virgin conscious, unrestrained Sprague-Dawley rats with long-term indwelling vascular catheters were studied. Mean arterial pressure (MAP) and heart rate were measured in response to continuous infusions of either vehicle (5% dextrose) or increasing concentrations of norepinephrine (25, 100, and 200 ng/kg/minute) before and after administration of NG-monomethyl-L-arginine (LNMMA), a specific inhibitor of EDRF synthesis.
Results:
Baseline MAP was lower in pregnant than in virgin rats (96 +/- 3 versus 105 +/- 3 mmHg; P < .05). Before LNMMA administration, the pregnant rats exhibited a significantly blunted pressor response to increasing concentrations of norepinephrine compared to that of virgin rats (P < .005). Given alone, LNMMA produced a greater increase in baseline MAP in virgin rats than in pregnant rats (rise in MAP of 44 +/- 2 versus 31 +/- 2 mmHg; P < .001). However, LNMMA abolished the blunted pressor response to norepinephrine in the pregnant animals and did not significantly affect the pressor response to norepinephrine in virgin rats. Heart rate responses to increasing concentrations of norepinephrine in the presence and absence of LNMMA were not significantly different in the two groups of animals.
Conclusion:
Stimulated EDRF production may contribute to the blunted pressor response to norepinephrine characteristic of pregnancy in the rat.