Cytosolic Phospholipase A2α 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 A 2 α (cPLA 2 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— cPLA 2 α gene–deficient mice (cPLA 2 α−/−) and wild-type mice (WT) were administered the NO synthesis inhibitor N 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 cPLA 2 α−/− after treatment. Bone marrow transplantation experiments showed that cPLA 2 α in blood cells and plasma eicosanoid concentrations were not involved in BP elevation by l-NAME treatment. Activation of cPLA 2 α and subsequent production of eicosanoids in the aortic endothelium but not in aortic smooth muscle cell, heart, or kidney was observed after l-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 cPLA 2 α−/−. Conclusion— These results suggest that endothelial cPLA 2 α may play a principal role in l-NAME-induced hypertension and may be a target molecule for maintaining endothelial function under NO inhibition.