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

The regulation of blood pressure during pregnancy involves several biologic al pathways. Candidate genes implicated in hypertensive diseases during pre gnancy include those of the renin-angiotensin system and nitric oxide synth ase (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 heter ozygous deficient for eNOS (Agt(2/2) Nos3(+/-)), four copies of Agt and hom ozygous deficient for eNOS (Agt(2/2) Nos3(+/-))]. Blood pressure measuremen ts of nulliparous females from mutant strains were compared with two common laboratory strains C57Bl6/J and SV129 throughout their first pregnancy. Se rum and urine analysis for the evaluation of renal and liver physiology wer e measured in the prepregnant state and during the third trimester of pregn ancy. Throughout pregnancy blood pressures in all mutant strains were highe r compared with controls. Agt(2/2) Nos3(+/-) showed the highest blood press ures and C57Bl6/J the lowest. Control mice, but not mutant mice, showed a s econd trimester decline in blood pressure. No immediate differences were no ted regarding behavioral characteristics, renal or liver function parameter s. Mice deficient for eNOS, mice with overexpression of Agt, and mice with mutations in both genes demonstrated higher blood pressure throughout pregn ancy. There was no evidence of renal dysfunction, liver dysfunction, or hem olysis among any of the strains studied. We conclude that Nos3 and Agt are important genes in the regulation of blood pressure during pregnancy.