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.


METHODS
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 N omega-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 N omega-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 N omega-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. N omega-monomethyl-L-arginine enhanced the angiotensin II responses in the pregnant, but not in the nonpregnant, rat hind limbs.


CONCLUSIONS
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.
Ahokas
R A
RA
Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38163.
Sibai
B M
BM
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values; D019323:omega-N-Methylarginine
D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine