Increased Expression of Angiotensin II Type 2 Receptors in the Solitary–Vagal Complex Blunts Renovascular Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 64; no. 4; pp. 777 - 783
• Main Authors: Blanch, Graziela Torres, Freiria-Oliveira, André Henrique, Speretta, Guilherme Fleury Fina, Carrera, Eduardo J, Li, Hongwei, Speth, Robert C, Colombari, Eduardo, Sumners, Colin, Colombari, Débora S.A
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.10.2014
• Subjects: Animals; Dependovirus - genetics; Gene Expression; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hypertension, Renovascular - genetics; Hypertension, Renovascular - metabolism; Male; Microscopy, Fluorescence; Peptidyl-Dipeptidase A - genetics; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 2 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Solitary Nucleus - metabolism; Vagus Nerve - metabolism; angiotensin-converting enzyme 2; angiotensin receptor blockers; baroreflex; angiotensin II
• DOI: 10.1161/HYPERTENSIONAHA.114.03188
• ISSN: 0194-911X

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.