Autocrine and Paracrine Function of Angiotensin 1–7 in Tissue Repair During Hypertension

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Abstract

BACKGROUND

Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin (Ang) II to generate Ang1–7, which mediates cellular actions through Mas receptors (MasR). Hypertension is accompanied by high or low circulating AngII levels and cardiac/renal injury. The purpose of this study is to explore (i) whether circulating AngII affects ACE2/MasR expressions in the hypertensive heart and kidney; and (ii) whether Ang1–7 regulates cardiac repair/remodeling responses through MasR during hypertension.

METHODS

In the first portion of the study, rats received either an AngII infusion (400ng/kg/min) for 4 weeks, leading to hypertension with high circulating AngII, or an aldosterone (ALDO, 0.75 μg/h) infusion for 4 weeks, leading to hypertension with low/normal circulating AngII. Cardiac and renal ACE2/MasR expressions were examined. We found that cardiac ACE2 was increased and MasR attenuated in both AngII and ALDO groups. However, renal ACE2 and MasR remained unchanged in both AngII- and ALDO-treated animals.

RESULTS

In the second portion, rats received AngII infusion with/without MasR antagonist (A779, 1mg/kg/day) for 4 weeks. The roles of MasR blockade in cardiac inflammation, fibrosis, apoptosis, and ventricular function were examined.

RESULTS

Chronic AngII infusion caused scattered cardiac injuries, and A779 cotreatment exacerbated cardiac injury, resulting in aggravated inflammatory, fibrogenic, and apoptotic responses compared with the AngII group. Cardiac function, however, was unaltered in the AngII and A779 groups.

CONCLUSIONS

ACE2 and MasR expressions in the hypertensive heart and kidney are not regulated by circulating AngII levels. Ang1–7 is involved in multiple repair responses, suggesting that therapeutic strategies aimed at administering Ang1–7 hold potential for the management of cardiac remodeling.

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