Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats.
Angiotensin-(ANG)-(1-7) is known by its central and peripheral actions, which mainly oppose the deleterious effects induced by accumulation of ANG II during pathophysiological conditions. In the present study we evaluated whether a chronic increase in ANG-(1-7) levels in the brain would modify the progression of hypertension. After DOCA-salt hypertension was induced for seven days, Sprague-Dawley rats were subjected to 14 days of intracerebroventricular (ICV) infusion of ANG-(1-7) (200 ng/h, DOCA-A7) or 0.9% sterile saline. As expected, on the 21st day, DOCA rats presented increased mean arterial pressure (MAP) (≈40%), and impaired baroreflex control of heart rate (HR) and baroreflex renal sympathetic nerve activity (RSNA) in comparison with that in normotensive control rats (CTL). These changes were followed by an overactivity of the cardiac sympathetic tone and reduction of the cardiac parasympathetic tone, and exaggerated mRNA expression of collagen type I (≈9-fold) in the left ventricle. In contrast, DOCA rats treated with ANG-(1-7) ICV had an improvement of baroreflex control of HR, which was even higher than that in CTL, and a restoration of the baroreflex control of RSNA, the balance of cardiac autonomic tone, and normalized mRNA expression of collagen type I in the left ventricle. Furthermore, DOCA-A7 had MAP lowered significantly. These effects were not accompanied by significant circulating or cardiac changes in angiotensin levels. Taken together, our data show that chronic increase in ANG-(1-7) in the brain attenuates the development of DOCA-salt hypertension, highlighting the importance of this peptide in the brain for the treatment of cardiovascular diseases.
National Institute of Science and Technology-Nanobiofar, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Priscila S
PS
Guimaraes
Nivia M
NM
Santiago
Carlos H
CH
Xavier
Elizabeth P P
EP
Velloso
Marco A P
MA
Fontes
Robson A S
RA
Santos
Maria Jose
MJ
Campagnole-Santos
D000803:Angiotensin I / Q000008:administration & dosage* / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D057967:Infusions, Intraventricular; D007668:Kidney / Q000294:innervation; D020547:Lateral Ventricles; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D000959:Antihypertensive Agents; D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D012333:RNA, Messenger; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000803:Angiotensin I; C118790:angiotensin I (1-7)