Nitric oxide synthase gene knockout mice do not become hypertensive during pregnancy

Objective: The purpose of this study was to test whether omitting the vasodilator nitric oxide that is derived from any 1 of the 3 isoforms of nitric oxide synthase results in hypertension during pregnancy. Study Design: We measured systolic blood pressure before, during, and after pregnancy using an automated tail cuff method in 3 mutant (gene knockout) mouse strains in which the gene for neuronal nitric oxide, inducible nitric oxide, or endothelial nitric oxide was disrupted by gene targeting. Results: In neuronal nitric oxide gene knockout mice (n = 10), blood pressure was 100 ± 3 mm Hg, not significantly different from 101 ± 3 mm Hg in matched wild-type control mice (n = 10). Pregnancy did not change blood pressure or heart rate in either group. In inducible nitric oxide gene knockout mice (n = 9), blood pressure was 110 ± 3 mm Hg, the same as in the wild-type control mice (110 ± 2 mm Hg; N = 14). Blood pressure was unaffected by pregnancy in either group of mice. However, heart rate was significantly less in knockout mice (647 ± 11 beats/min vs 666 ± 9 beats/min; P< .005); this difference persisted through pregnancy. In endothelial nitric oxide gene knockout mice (n = 8), blood pressure was higher before pregnancy (114 ± 4 mm Hg vs 103 ± 4 mm Hg; P< .05) than in wild-type control mice (n = 9), but this difference disappeared during pregnancy, returning only after delivery. Heart rates were not different before pregnancy and were unaffected by pregnancy. Conclusion: There was no apparent increase in systolic blood pressure in any of the 3 nitric oxide synthase gene knockout strains during pregnancy compared to the wild-type control mice. This suggests that, at least in the mouse, genetic deficiency of any 1 isoform of nitric oxide synthase does not result in pregnancy-induced hypertension. (Am J Obstet Gynecol 2001;185:1198-203.)