Document Detail

Nitric oxide synthase gene knockout mice do not become hypertensive during pregnancy.
MedLine Citation:
PMID:  11717657     Owner:  NLM     Status:  MEDLINE    
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.
E G Shesely; C Gilbert; G Granderson; C D Carretero; O A Carretero; W H Beierwaltes
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  185     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-21     Completed Date:  2001-12-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1198-203     Citation Subset:  AIM; IM    
Hypertension and Vascular Research Division, Henry Ford Hospital, Case Western Reserve University Detroit Medical Campus, Mich 48202-2689, USA.
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MeSH Terms
Blood Pressure / physiology*
Mice, Knockout / genetics
Nitric Oxide Synthase / deficiency*,  genetics,  physiology
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Pregnancy, Animal / physiology*
Grant Support
Reg. No./Substance:
EC Oxide Synthase; EC Oxide Synthase Type I; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, mouse; EC protein, mouse; EC protein, mouse

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