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

Autor(es)

Blanch, Graziela Torres ^[1] ; Freiria-Oliveira, Andre Henrique ^[1] ; Fina Speretta, Guilherme Fleury ^[1] ; Carrera, Eduardo J. ^[2] ; Li, Hongwei ^[3] ; Speth, Robert C. ^{[4, 5, 2]} ; Colombari, Eduardo ^[1] ; Sumners, Colin ^{[4, 5]} ; Colombari, Debora S. A. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Sch Dent, Dept Physiol & Pathol, Sao Paulo - Brazil

^[2] Nova SE Univ, Coll Pharm, Dept Pharmaceut Sci, Ft Lauderdale, FL 33314 - USA

^[3] Southern Med Univ, Sch Biotechnol, Guangzhou, Guangdong - Peoples R China

^[4] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL - USA

^[5] Univ Florida, Coll Med, McKnight Brain Inst, Gainesville, FL - USA

• Tipo de documento: Artigo Científico
• Fonte: Hypertension; v. 64, n. 4, p. 777+, OCT 2014.
• Citações Web of Science: 21

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. (AU)

• Processo FAPESP: 13/50121-9 - UNESP-UF: Hypertension Research Exchange Program
• Beneficiário: Eduardo Colombari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/50770-1 - Mecanismos neurais de regulação do equilíbrio hidroeletrolítico e controle cardiorrespiratório
• Beneficiário: José Vanderlei Menani
• Modalidade de apoio: Auxílio à Pesquisa - Temático