Enhanced blood pressure variability in eNOS knockout mice

It has been shown previously that endogenous nitric oxide can buffer arteri al blood pressure variability in dogs and rats. In these former studies, al l isoforms of the nitric oxide synthase were blocked pharmacologically and an increased blood pressure variability was observed. Thus the question as to which isoform of the nitric oxide synthase is responsible for the blood pressure buffering effect of endogenous nitric oxide remains unraveled. In the present study, we therefore compared blood pressure variability in knoc kout mice that lack specifically the gene for endothelial nitric oxide synt hase with their respective wild-type controls. One day after carotid artery cannulation, blood pressure was recorded in these conscious mice. During r esting conditions, blood pressure variability was markedly enhanced in knoc kout mice compared with wild-type mice (10.5+/-1.5 mm Hg-2 vs 6.0+/-0.8 mm Hg-2, P<0.05), Power spectral analysis revealed that this increase in blood pressure variability is manifested at low frequencies that range from 0.05 to 0.40 s(-1) (Hz) (5.1+/-1.0 mm Hg-2 vs 2.5+/-0.5 mm Hg-2, P<0.05). On th e basis of these results, we conclude that the blood pressure buffering eff ect of endogenous nitric oxide is mediated by the endothelial isoform of th e nitric oxide synthase. In addition, endothelial nitric oxide is most effe ctive in buffering blood pressure oscillations at frequencies that range fr om 0.05 to 0.40 s(-1) (Hz) in conscious mice.