The role of nitric oxide in the modulation of vascular tone in normal pregnancy and preeclampsia

OBJECTIVE: Peripheral arterial resistance falls during normal pregnancy and is increased in severe preeclampsia. The aim of this study was to determine the role of nitric oxide (NO) in these changes. STUDY DESIGN: Twenty healthy nonpregnant women (NP), 20 normotensive primigravidae (P), and 15 primigravidae with preeclampsia on no treatment (PE) were studied. Forearm blood flow (FBF, ml/100ml/min) responses to brachial artery infusion of angiotensin II (All) and NG-monomelhyl-L-arginine (L-NMMA, a NOS inhibitor) were measured by plethysmography. After 30 minutes of saline, All was infused at 3 doses (2, 4, and 8ng/min) for 5 minutes each, and L-NMMA infused (200, 400, and 800ug/min). In P and PE, noradrenaline (Nadr, 5-10ng/min) was infused to reduce FBF to NP levels, and was then coinfused with All and L-NMMA. Drug responses were compared as mean(SE) area under the dose-response curves (AUCs), and analysed by ANOVA and 2 sample t tests. RESULTS: Pregnant subjects showed a blunted constrictor response to All, and an enhanced response to L-NMMA when compared to NP. Preeclamptic subjects showed an enhanced response to All but no difference in response to LNMMA when compared to P. NP (SE) P (SE) PE (SE) Systolic BP 123 (3) 130 (2) 161 (3)+ + + Diastolic BP 65(1) 69 (2) 93 (2)+ + + Gestation (wks) - 34 (1) 36 (1) Baseline FBF 2.9 (0.3) 3.6 (0.3)* 4.2 (0.5) FBF with NAdr - 2.9 (0.3) 3.3 (0.4) AUC All 125 (11) 79 (7)*** 103 (8)+ AUC LNMMA 60 (7) 89 (8)** 73 (10) (* P vs NP + P vs. PE;+ p<0,05,+ +p<0.01,+ + + P<0.001) CONCLUSION: Enhanced NO activity may contribute to the fall in peripheral arterial resistance during normal pregnancy. Decreased NO activity does not appear to be the principal cause of the increased vascular tone seen in preeclampsia.