Efeitos da terapia gênica com a óxido nítrico sintase endotelial em camundongos com hipertensão renovascular 2R1C

Abstract

Several studies have demonstrated that gene therapy is an effective approach to prevention and treatment of arterial hypertension (ÁH). Therefore, the goal of this study was to evaluate the effects of endothelial nitric oxide synthase (eNOS) gene therapy in the development of two kidney-one clip (2K1C) renovascular hypertension and baroreflex (BR) in mice. C57 male mice received a stainless steel clip (0,12 mm) in the left renal artery or were submitted to a ficticious surgery (sham-SH). In this same day, the animals received an intravenous injection of adenovirus expressing ßgalactosidade (ßgal), eNOS (10 µL, 1012 pfu/mL) or glicerol (10 µL). After 2 weeks, the animals were anesthetized and catheters were implanted in jugular vein and carotidy artery to drug injection and mean arterial pressure (MAP) and heart rate (HR) measurements. The baroreflex was tested in conscious animals through in bolus injection of phenylephrine (PHE-48 µg/Kg) and sodium nitroprusside (SNP24 µg/Kg) and evaluated through the mean gain to bradycardic and tachycardic reflex responses in arterial pressure variations (5-25 mmHg). At the end of the experiments, the heart and kidneys were removed and weighed to hypertrophy analysis.