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Author Grobe, Justin L
Title The role of angiotension-(1-7) in cardiovascular physiology
book jacket
Descript 133 p
Note Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 2997
Adviser: Michael J. Katovich
Thesis (Ph.D.)--University of Florida, 2006
Heart failure (HF) is a devastating condition that impacts our society emotionally, physiologically, and fiscally, and it is a growing problem in the United States. Aberrant activity of the renin-angiotensin hormone system (RAS) has been implicated as a causative factor in HF. Recently, a new angiotensin converting enzyme 2 (ACE2) was recognized, which catalyzes the degradation of the active angiotensin II (Ang II) hormone to angiotensin-(1-7) (Ang-(1-7)). Studies into the actions of ACE2 have led to the concept that Ang-(1-7) may act as an active, endogenous inhibitor of the RAS. Interestingly, investigations into the mechanisms of action of ACE inhibitors and AT1R antagonists have revealed that both of these treatments result in increased circulating levels of Ang-(1-7). Some have therefore hypothesized that pharmacological inhibitors of the RAS may provide cardioprotective effects through the actions of Ang-(1-7)
The present studies were designed to characterize the cardioprotective actions of Ang-(1-7) in various models of cardiac remodeling. The protective effect of Ang-(1-7) was evaluated in Ang II-infusion, mineralocorticoid, and beta-adrenergic models of cardiac remodeling. Further, due to gender differences in the development and progression of heart failure, the protective actions of Ang-(1-7) were evaluated in intact and ovariectomized female rats. Cardiac remodeling was inhibited by Ang-(1-7), with specific effects determined by the type of stimulus, and estrogens were determined to play an important role in regulating tissue sensitivity to Ang-(1-7)
From these findings, it was concluded that Ang-(1-7) has specific actions in the cardiovascular system, some of which oppose the actions of its precursor, Ang II. In addition, our results lead us to hypothesize that estrogen replacement therapy during menopause may predispose women to cardiovascular diseases through decreased tissue sensitivity to the protective Ang-(1-7) hormone. Future studies should more directly characterize the effects of estrogens on cardiac tissue, and further elucidate the tissue-level and intracellular signaling mechanisms of Ang-(1-7). Our results indicate that Ang-(1-7) may represent a new, unexploited class of targets for pharmacological intervention before and during HF
School code: 0070
Host Item Dissertation Abstracts International 67-06B
Subject Health Sciences, Pharmacology
Biology, Physiology
Alt Author University of Florida
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