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PMID: 8917564 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Elevated blood pressures in mice lacking endothelial nitric oxide synthase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 13176-81

Shesely EG, Maeda N, Kim HS, Desai KM, Krege JH, Laubach VE, Sherman PA, Sessa WC, Smithies O

Abstract

Nitric oxide produced in endothelial cells affects vascular tone. To investigate the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation, we have generated mice heterozygous (+/-) or homozygous (-/-) for disruption of the eNOS gene. Immunohistochemical staining with anti-eNOS antibodies showed reduced amounts of eNOS protein in +/- mice and absence of eNOS protein in -/- mutant mice. Male or female mice of all three eNOS genotypes were indistinguishable in general appearance and histology, except that -/- mice had lower body weights than +/+ or +/- mice. Blood pressures tended to be increased (by approximately 4 mmHg) in +/- mice compared with +/+, while -/- mice had a significant increase in pressure compared with +/+ mice (approximately 18 mmHg) or +/- mice (approximately 14 mmHg). Plasma renin concentration in the -/- mice was nearly twice that of +/+ mice, although kidney renin mRNA was modestly decreased in the -/- mice. Heart rates in the -/- mice were significantly lower than in +/- or +/+ mice. Appropriate genetic controls show that these phenotypes in F2 mice are due to the eNOS mutation and are not due to sequences that might differ between the two parental strains (129 and C57BL/6J) and are linked either to the eNOS locus or to an unlinked chromosomal region containing the renin locus. Thus eNOS is essential for maintenance of normal blood pressures and heart rates. Comparisons between the current eNOS mutant mice and previously generated inducible nitric oxide synthase mutants showed that homozygous mutants for the latter differ in having unaltered blood pressures and heart rates; both are susceptible to lipopolysaccharide-induced death.

MeSH Terms
Analysis of Variance Animals Blood Pressure Cattle Chimera DNA Primers Endothelium, Vascular/enzymology Female Genotype Heterozygote Hypertension/genetics,physiopathology Isoenzymes/deficiency,genetics Kidney/enzymology Lipopolysaccharides/toxicity Male Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase/deficiency,genetics Polymerase Chain Reaction RNA, Messenger/metabolism Renin/biosynthesis,blood Stem Cells Transcription, Genetic
Chemicals
DNA Primers Isoenzymes Lipopolysaccharides RNA, Messenger Nitric Oxide Synthase Renin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Shesely E G
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill 27599, USA.
Maeda N
Kim H S
Desai K M
Krege J H
Laubach V E
Sherman P A
Sessa W C
Smithies O
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.13176
Published
1996-11-12
Pages
13176-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24066
Subset
IM
Grants
NHLBI NIH HHS · HL03470 · United States
NIGMS NIH HHS · R01 GM020069 · United States
NHLBI NIH HHS · R01 HL049277 · United States
NHLBI NIH HHS · HL49277 · United States
Wellcome Trust · United Kingdom
NIGMS NIH HHS · F31 GM020069 · United States
NIGMS NIH HHS · GM20069 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.23.13176 PMC Full Text View journal details
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