Cytosolic Phospholipase A 2 α Contributes to Blood Pressure Increases and Endothelial Dysfunction Under Chronic NO Inhibition

Objective— Nitric oxide (NO) is an important modulator of cardiovascular function. In this study, we examined whether cytosolic phospholipase A2 α (cPLA2 α), an initial enzyme in the arachidonic acid pathway, is involved in blood pressure (BP) elevation in a murine model of chronic NO inhibition.Methods and Results— cPLA2 α gene–deficient mice (cPLA2 α−/−) and wild-type mice (WT) were administered the NO synthesis inhibitorN ω -nitro-l -arginine methyl ester (l -NAME) for 4 weeks. Before treatment, BP was comparable in both groups; it increased significantly in the WT but not in the cPLA2 α−/− after treatment. Bone marrow transplantation experiments showed that cPLA2 α in blood cells and plasma eicosanoid concentrations were not involved in BP elevation byl -NAME treatment. Activation of cPLA2 α and subsequent production of eicosanoids in the aortic endothelium but not in aortic smooth muscle cell, heart, or kidney was observed afterl -NAME treatment. Aortic ring assays revealed that endothelial function was comparable in both groups of mice before treatment.l -NAME treatment disturbed endothelial function in WT but not in cPLA2 α−/−.Conclusion— These results suggest that endothelial cPLA2 α may play a principal role inl -NAME-induced hypertension and may be a target molecule for maintaining endothelial function under NO inhibition.