Enhanced blood pressure variability in eNOS knockout mice.

It has been shown previously that endogenous nitric oxide can buffer arterial blood pressure variability in dogs and rats. In these former studies, all 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 knockout mice that lack specifically the gene for endothelial nitric oxide synthase with their respective wild-type controls. One day after carotid artery cannulation, blood pressure was recorded in these conscious mice. During resting conditions, blood pressure variability was markedly enhanced in knockout mice compared with wild-type mice (10.5+/-1.5 mm Hg2 vs 6.0+/-0.8 mm Hg2, 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 Hg2 vs 2.5+/-0.5 mm Hg2, P<0.05). On the basis of these results, we conclude that the blood pressure buffering effect of endogenous nitric oxide is mediated by the endothelial isoform of the nitric oxide synthase. In addition, endothelial nitric oxide is most effective in buffering blood pressure oscillations at frequencies that range from 0.05 to 0.40 s-1 (Hz) in conscious mice.