Nitric oxide synthase gene knockout mice do not become hypertensive duringpregnancy

OBJECTIVE: The purpose of this study was to test whether omitting the vasod ilator 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 pressu re 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 pr essure or heart rate in either group. In inducible nitric oxide gene knocko ut mice (n = 9), blood pressure was 110 +/- 3 mm Hg, the same as in the wil d-type control mice (110 +/- 2 mm Hg; n = 14). Blood pressure was unaffecte d by pregnancy in either group of mice. However, heart rate was significant ly less in knockout mice (647 +/- 11 beats/min vs 666 +/- 9 beats/min; P < .005); this difference persisted through pregnancy. In endothelial nitric o xide 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 mi ce (n = 9), but this difference disappeared during pregnancy, returning onl y 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 an y of the 3 nitric oxide synthase gene knockout strains during pregnancy com pared to the wild-type control mice. This suggests that, at least in the mo use, genetic deficiency of any 1 isoform of nitric oxide synthase does not result in pregnancy-induced hypertension.