Analysis in vivo and in vitro effect of apocynin on endothelial dysfunction in spontaneously hypertensive rats (SHR)

Abstract

Chronic treatment with NADPH oxidase inhibitors reduces the arterial pressure of SHR. As the main source of superoxide anion in the aorta, the activity of NADPH oxidase is associated with decreased NO bioavailability and uncoupling of eNOS. The purpose of this study will test the hypothesis that apocynin (NADPH oxidase inhibitor) reverses the endothelial dysfunction that occurs during the development of hypertension in SHR. For this purpose, normotensive Wistar and SHR are treated with apocynin (30 mg / kg/ day, po) from the fourth through the tenth week of life. During treatment, systolic blood pressure of animals will be checked by tail plethysmography. In vivo experiments will be conducted to assess possible changes in the baseline blood pressure (average systolic and diastolic) and heart rate, and the hypotensive responses stimulated by acetylcholine and sodium nitroprusside. In vitro experiments will be performed to determine if the treatment with apocynin promotes changes in [Ca +2] intracellular, production of NO and reactive oxygen species in endothelial cells (flow cytometry), and the protein expression for potassium channels and soluble guanylate cyclase in the aorta (Western Blott) of these animals. (AU)