Nitric oxide activity in the peripheral vasculature during normotensive and preeclamptic pregnancy.
Anumba DO., Robson SC., Boys RJ., Ford GA.
We investigated the role of nitric oxide (NO) in the vascular resistance changes of normotensive and preeclamptic pregnancy. Forearm blood flow (FBF) responses to brachial artery infusion of N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, and angiotensin II (ANG II), an NO-independent vasoconstrictor, were determined by plethysmography in 20 nonpregnant women, 20 normotensive primigravidae, and 15 primigravidae with untreated preeclampsia. In pregnant subjects, FBF was reduced to nonpregnancy levels by infusion of norepinephrine (NE), which was then coinfused with ANG II (2, 4, and 8 ng/min) and L-NMMA (200, 400, and 800 microgram/min) each for 5 min. In separate studies, responses to NE (20, 50, and 100 ng/min) were determined in 8 nonpregnant women, with FBF elevated to pregnancy levels by concomitant infusion of glyceryl trinitrate, and 10 pregnant women. Vasoconstrictor responses to L-NMMA were increased in pregnant compared with nonpregnant subjects [mean +/- SE summary measure (in arbitrary units): 60 +/- 7 vs. 89 +/- 8, respectively; P < 0.01], whereas responses to ANG II were blunted (125 +/- 11 vs. 79 +/- 7, respectively; P < 0.001). Compared with normotensive pregnant subjects, preeclamptic subjects had an enhanced response to ANG II (79 +/- 7 vs. 103 +/- 8, respectively; P < 0.05) but no difference in response to L-NMMA (89 +/- 8 vs. 73 +/- 10, respectively; P = 0.30). Responses to NE were similar in pregnant and nonpregnant subjects (110 +/- 20 vs. 95 +/- 33, respectively; P = 0.66). During the third trimester of pregnancy, forearm constrictor responses to L-NMMA are increased. The responses to NE are unchanged, whereas responses to ANG II are blunted. Increased NO activity contributes to the fall in peripheral resistance. In preeclampsia, forearm constrictor responses to ANG II but not L-NMMA are increased compared with those in normal pregnancy. Changes in vascular NO activity are unlikely to account for the increased vascular tone in this condition.