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.


METHODS
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.


CONCLUSIONS
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.
Shesely
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EG
Hypertension and Vascular Research Division, Henry Ford Hospital, Case Western Reserve University Detroit Medical Campus, Mich 48202-2689, USA.
Gilbert
C
C
Granderson
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G
Carretero
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CD
Carretero
O A
OA
Beierwaltes
W H
WH
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse