This study investigates the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation by generating mice with heterozygous (+/−) or homozygous (−/−) disruptions of the eNOS gene. Immunohistochemical staining confirmed the absence of eNOS protein in −/− mice. Blood pressures were significantly elevated in +/− mice compared to wild-type (+/+) mice, and −/− mice showed a more pronounced increase in blood pressure compared to +/− and +/+ mice. Plasma renin concentration was nearly twice as high in −/− mice, despite a modest decrease in kidney renin mRNA. Heart rates were significantly lower in −/− mice. The phenotypes in F2 mice were attributed to the eNOS mutation rather than genetic differences between the parental strains. The study also compared eNOS mutant mice with previously generated inducible nitric oxide synthase (iNOS) mutant mice, finding that both lack significant changes in blood pressure and heart rate but are susceptible to lipopolysaccharide-induced death. The results suggest that eNOS is essential for maintaining normal blood pressure and heart rates.This study investigates the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation by generating mice with heterozygous (+/−) or homozygous (−/−) disruptions of the eNOS gene. Immunohistochemical staining confirmed the absence of eNOS protein in −/− mice. Blood pressures were significantly elevated in +/− mice compared to wild-type (+/+) mice, and −/− mice showed a more pronounced increase in blood pressure compared to +/− and +/+ mice. Plasma renin concentration was nearly twice as high in −/− mice, despite a modest decrease in kidney renin mRNA. Heart rates were significantly lower in −/− mice. The phenotypes in F2 mice were attributed to the eNOS mutation rather than genetic differences between the parental strains. The study also compared eNOS mutant mice with previously generated inducible nitric oxide synthase (iNOS) mutant mice, finding that both lack significant changes in blood pressure and heart rate but are susceptible to lipopolysaccharide-induced death. The results suggest that eNOS is essential for maintaining normal blood pressure and heart rates.