Central endogenous angiotensin-(1-7) protects against aldosterone/NaCl-induced hypertension in female rats

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 305; no. 5; pp. H699 - H705
• Main Authors: Xue, Baojian, Zhang, Zhongming, Johnson, Ralph F, Guo, Fang, Hay, Meredith, Johnson, Alan Kim
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2013
• Subjects: ACE inhibitors; Aldosterone - adverse effects; Aldosterone - pharmacology; Angiotensin I - metabolism; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Brain; Cardiovascular Neurohormonal Regulation; Disease Models, Animal; Female; Hormones; Hypertension; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - prevention & control; NADPH Oxidases - metabolism; Peptide Fragments - metabolism; Peptidyl-Dipeptidase A - metabolism; Polymerase chain reaction; Proto-Oncogene Proteins - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Estrogen - metabolism; Receptors, G-Protein-Coupled - metabolism; Renin-Angiotensin System - physiology; RNA, Messenger - metabolism; Rodents; Sex Factors; Sodium Chloride - adverse effects; Sodium Chloride - pharmacology; blood pressure; aldosterone; angiotensin-(1–7); central nervous system
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00193.2013

In comparison to male rodents, females are protected against angiotensin (ANG) II- and aldosterone (Aldo)-induced hypertension. However, the mechanisms underlying this protective effect are not well understood. ANG-(1-7) is formed from ANG II by angiotensin-converting enzyme 2 (ACE2) and has an antihypertensive effect in the central nervous system (CNS). The present study tested the hypothesis that central ANG-(1-7) plays an important protective role in attenuating the development of Aldo/NaCl-hypertension in female rats. Systemic infusion of Aldo into intact female rats with 1% NaCl as their sole drinking fluid resulted in a slight increase in blood pressure (BP). Intracerebroventricular (icv) infusion of A-779, an ANG-(1-7) receptor (Mas-R) antagonist, significantly augmented the pressor effects of Aldo/NaCl. In contrast, systemic Aldo/NaCl induced a significant increase in BP in ovariectomized (OVX) female rats, and central infusion of ANG-(1-7) significantly attenuated this Aldo/NaCl pressor effect. The inhibitory effect of ANG-(1-7) on the Aldo/NaCl pressor effect was abolished by concurrent infusion of A-779. RT-PCR analyses showed that there was a corresponding change in mRNA expression of several renin-angiotensin system components, estrogen receptors and an NADPH oxidase subunit in the lamina terminalis. Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1-7)/Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension.