Enhanced endothelium-derived relaxing factor activity in pregnant, spontaneously hypertensive rats

Pregnancy is normally associated with vasodilation that, in hypertensive animals such as the spontaneously hypertensive rat, causes a profound decrease in blood pressure. To test the possibility that enhanced basal endothelium-derived relaxing factor activity has a role in the vasodilation of pregnancy, we measured the changes in mean arterial pressure and heart rate induced by NG-monomethyl-L-arginine, a specific inhibitor of endothelium-derived relaxing factor synthesis, in conscious nonpregnant and pregnant (postmating day 20 to 21) normotensive Wistar-Kyoto and spontaneously hypertensive rats. NG-monomethyl-L-arginine caused similar dose-dependent increases in mean arterial pressure in nonpregnant and pregnant Wistar-Kyoto rats, but the accompanying decrease in heart rate was significantly greater in nonpregnant rats than in pregnant ones. In the spontaneously hypertensive rats, NG-monomethyl-L-arginine caused significantly greater dose-dependent increases in mean arterial pressure in pregnant compared with nonpregnant rats; there were no differences in the decreases in heart rate. These pressor responses were partially reversed by excess L-arginine but not D-arginine. Indomethacin had no effect on the pressor response to NG-monomethyl-L-arginine or the depressor response to L-arginine after NG-monomethyl-L-arginine. Therefore basal endothelium-derived relaxing factor plays a role in vascular tone and blood pressure regulation in vivo, and pregnancy may be associated with enhanced basal endothelium-derived relaxing factor activity in the hypertensive spontaneously hypertensive rats.