title: Increased expression of angiotensin II type 2 receptors in the solitary-vagal complex blunts renovascular hypertension.
abstract: 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.
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Graziela Torres
authors: GT
authors: Blanch
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: André Henrique
authors: AH
authors: Freiria-Oliveira
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Guilherme Fleury Fina
authors: GF
authors: Speretta
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Eduardo J
authors: EJ
authors: Carrera
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Hongwei
authors: H
authors: Li
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Robert C
authors: RC
authors: Speth
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.).
authors: Eduardo
authors: E
authors: Colombari
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.). deborac@foar.unesp.br csumners@ufl.edu.
authors: Colin
authors: C
authors: Sumners
authors: From the Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil (G.T.B., A.H.F.-O., G.F.F.S., E.C., D.S.A.C.); Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL (E.J.C., R.C.S.); School of Biotechnology, Southern Medical University, Guangzhou, China (H.L.); and Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville (C.S., R.C.S.). deborac@foar.unesp.br csumners@ufl.edu.
authors: Débora S A
authors: DS
authors: Colombari
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D049452:Green Fluorescent Proteins; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
keywords: angiotensin II; angiotensin receptor blockers; angiotensin-converting enzyme 2; baroreflex