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: Graziela Torres Blanch, André Henrique Freiria-Oliveira, Guilherme Fleury Fina Speretta, Eduardo J Carrera, Hongwei Li, Robert C Speth, Eduardo Colombari, Colin Sumners, Débora S A Colombari
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 64 Issue 4 Pg. 777-83 (Oct 2014) ISSN: 1524-4563 [Electronic] United States
• PMID: 24958505 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Green Fluorescent Proteins
• Peptidyl-Dipeptidase A
• Ace2 protein, rat
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2
• Animals
• Dependovirus (genetics)
• Gene Expression
• Green Fluorescent Proteins (genetics, metabolism)
• Hypertension, Renovascular (genetics, 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)