Title: Nitric Oxide Synthase and Soluble Guanylyl Cyclase Mediate Endothelial Responses in Aged Female Endothelial Nitric Oxide Synthase (eNOS)‐Deficient Mice
Abstract: We have shown previously that endothelial responses are normal in adult heterozygous eNOS deficient male and female mice and with aging endothelial function is markedly impaired in male eNOS+/−, but not female eNOS+/−, mice. The goal of the present study was to determine whether the preserved responses observed in aged female heterozygous eNOS+/− mice are due to NOS‐ and soluble guanylyl cyclase (sGC)‐dependent mechanisms. Endothelium‐dependent and ‐independent responses of carotid arteries from adult (6 months of age) and old (22–24 months of age) female eNOS+/+ and eNOS +/− mice were examined in the presence of vehicle (saline), L‐NNA (a NOS inhibitor), or ODQ (an inhibitor of sGC). Carotid artery responses to acetylcholine were similar (P>0.05) in adult and old female eNOS +/+ and eNOS+/− mice and were significantly inhibited (P<0.05) by L‐NNA and ODQ. Responses to nitroprusside were also similar in both groups of mice and were inhibited (P<0.05) by ODQ but not L‐NNA. The degree of inhibition produced by L‐NNA and/or ODQ was similar (P>0.05) in adult and old mice irrespective of genotype. These findings demonstrate that endothelial responses in old female eNOS+/− mice are not affected by aging and despite a 60% reduction in eNOS protein expression maintain their dependency on NOS and sGC. Support or Funding Information Supported by NIH HL‐089884 and HL‐107632.