Induction of Angiotensin-Converting Enzyme and Activation of the Renin–Angiotensin System Contribute to 20-Hydroxyeicosatetraenoic Acid–Mediated Endothelial Dysfunction

摘要: Objective— 20-hydroxyeicosatetraenoic acid (20-HETE) promotes endothelial dysfunction by uncoupling NO synthase, stimulating O2− production, and reducing bioavailability. Moreover, 20-HETE–dependent vascular hypertension are associated with upregulation of the renin–angiotensin system This study was undertaken to examine contribution 20-HETE actions in endothelium. Methods Results— In cells, induced angiotensin-converting enzyme (ACE) mRNA levels increased ACE protein activity 2- 3-fold; these effects were negated addition antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic (20 HEDE). expression kinase C independent epidermal growth factor receptor tyrosine IκB β dependent. short interfering RNA abolished 20-HETE–mediated inhibition production stimulation generation, whereas angiotensin II type 1 attenuated 40%. 20-HETE–stimulated 20-HEDE lisinopril losartan. Importantly, impairment acetylcholine-induced relaxation rat renal interlobar arteries also losartan. Conclusion— These results indicate that activation contribute cell further enforce notion excessive within vasculature leads via mechanisms include induction ACE, thus, perpetuating an increase which, together 20-HETE, dysfunction.