Alterations in endothelial nitric oxide synthase activity and their relevance to blood pressure.

Among all physiologic functions of nitric oxide (NO) known so far, NO-dependent regulation of vascular tone is one of the most important. Under physiological conditions vascular NO is mainly generated by endothelial NO-synthase (eNOS), the major isoform of NOS in the cardiovascular system. NO produced in vascular endothelial cells displays complex physiologic activities considered to be vasoprotective.

Contribution of cyclooxygenase-1-dependent prostacyclin synthesis to bradykinin-induced dermal extravasation.

Background: Non-allergic angioedema is a potentially life-threatening condition caused by accumulation of bradykinin and subsequent activation of bradykinin type 2 receptors (B2). Since COX activity plays a pivotal role in B2 signaling, the aim of this study was to determine which prostaglandins are the key mediators and which COX, COX-1 or COX-2, is predominantly involved.

Methods: We used Miles assays to assess the effects of inhibitors of COX, 5-lipoxygenase, epoxyeicosatrienoic acid generation, cytosolic phospholipase Aα and a variety of prostaglandin receptor antagonists on bradykinin-induced dermal extravasation in C57BL/6 and COX-1-deficient mice (COX-1).