Blood pressure control in eNOS knock-out mice: comparison with other species under NO blockade

Changes in arterial blood pressure (ABP) lead to changes in vascular shear stress. This mechanical stimulus increases cytosolic Ca2+ in endothelial ce lls, which in turn activates the endothelial isoform of the nitric oxide sy nthase. The subsequently formed NO reaches the adjacent vascular smooth mus cle cells, where it reduces vascular resistance in order to maintain ABP at its initial level. Thus, NO may play an important role as a physiological blood pressure buffer. Previous data on the importance of eNOS for blood pr essure control are reviewed with special emphasis on the fact that endogeno us nitric oxide can buffer blood pressure variability (BPV) in dogs, rats a nd mice. In previous studies where all isoforms of the nitric oxide synthas e were blocked pharmacologically, increases in blood pressure and variabili ty were observed. Thus, we set out to clarify which isoform of the nitric o xide synthase is responsible for this BPV controlling effect. Hence, blood pressure control was studied in knock-out mice lacking specifically the gen e for endothelial nitric oxide synthase with their respective wild-type con trols. One day after surgery, under resting conditions, blood pressure was increased by 47 mmHg (P < 0.05), heart rate was lower (-77 beats min(-1), P < 0.05), and BPV doubled (P < 0.05). Based on these results, we conclude t hat chronic blood pressure levels are influenced by eNOS and that there is a blood pressure buffering effect of endogenous nitric oxide which is media ted by the endothelial isoform of the nitric oxide synthase.