Endothelial-derived nitric oxide and angiotensinogen: blood pressure and metabolism during mouse pregnancy

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 ( Agt 2/2 ), and mutations in both genes [four copies of Agt and heterozygous deficient for eNOS (Agt 2/2 Nos3 +/ ), four copies of Agt and homozygous deficient for eNOS ( Agt 2/2 Nos3 / )]. 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. Agt 2/2 Nos3 / 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