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1 Department of Obstetrics and Gynecology and 2 Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
The regulation of blood pressure during pregnancy involves
several biological pathways. Candidate genes implicated in hypertensive diseases during pregnancy include those of the renin-angiotensin system
and nitric oxide synthase (NOS). We evaluated blood pressure and
metabolic characteristics during pregnancy in mutant mice. These
included mice with a null mutation in the endothelial NOS (eNOS) gene
(Nos3
/), four copies of the angiotensinogen
gene (Agt2/2), and mutations in both genes
[four copies of Agt and heterozygous deficient
for eNOS (Agt2/2Nos3+/),
four copies of Agt and homozygous deficient for
eNOS (Agt2/2Nos3/)].
Blood pressure measurements of nulliparous females from mutant strains
were compared with two common laboratory strains C57Bl6/J and SV129
throughout their first pregnancy. Serum and urine analysis for the
evaluation of renal and liver physiology were measured in the
prepregnant state and during the third trimester of pregnancy. Throughout pregnancy blood pressures in all mutant strains were higher
compared with controls.
Agt2/2Nos3/ showed the highest
blood pressures and C57Bl6/J the lowest. Control mice, but not mutant
mice, showed a second trimester decline in blood pressure. No immediate
differences were noted regarding behavioral characteristics, renal or
liver function parameters. Mice deficient for eNOS, mice with
overexpression of Agt, and mice with mutations in both genes
demonstrated higher blood pressure throughout pregnancy. There was no
evidence of renal dysfunction, liver dysfunction, or hemolysis among
any of the strains studied. We conclude that Nos3 and
Agt are important genes in the regulation of blood pressure
during pregnancy.
nitric oxide synthase gene Nos3
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