Increased expression of angiotensin II type 2 receptors in the solitary-vagal complex blunts renovascular hypertension

Resumo

Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin–angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary–vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip renovascular hypertension. Three weeks later, rats were microinjected in the solitary–vagal complex with either an adenoassociated virus to increase the expression of angiotensin type 2 receptors or with a control vector. We observed that increasing angiotensin type 2 receptor expression in the solitary–vagal complex attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex and the increase in the low-frequency component of systolic blood pressure observed in renovascular hypertensive rats. Furthermore, an observed decrease in mRNA levels of angiotensin-converting enzyme 2 in the solitary–vagal complex of renovascular hypertensive rats was restored to control levels after viral-mediated increases in angiotensin type 2 receptors at this site. Collectively, these data demonstrate specific and beneficial effects of angiotensin type 2 receptors via the brain of hypertensive rats and suggest that central angiotensin type 2 receptors may be a potential target for therapeutics in renovascular hypertension.

Descrição

Palavras-chave

Angiotensin II, Angiotensin-converting enzyme 2, Angiotensin receptor blockers, Baroreflex

Citação

BLANCH, Graziela Torres; FREIRIA-OLIVEIRA, André Henrique; SPERETTA, Guilherme Fleury Fina; CARREIRA, Eduardo J.; HONGWEI, Li; SPETH, Robert C.; COLOMBARI, Eduardo; SUMNERS, Colin; COLOMBARI, Débora S. A. Increased expression of angiotensin ii type 2 receptors in the solitary-vagal complex blunts renovascular hypertension. Hypertension, Dallas, v. 64, p. 777-783, Oct. 2014.