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Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats

Choisy, Stéphanie C.; Choisy, Stéphanie C.; Kim, Shang-Jin; Hancox, Jules C.; Jones, Sandra A.; James, Andrew F.

Authors

Stéphanie C. Choisy

Stéphanie C. Choisy

Shang-Jin Kim

Jules C. Hancox

Andrew F. James

Abstract

Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin–angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar- Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy.

Journal Article Type Article
Publication Date 2015-01
Journal Physiological reports
Print ISSN 2051-817x
Electronic ISSN 2051-817X
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 3
Issue 1
Article Number e12274
Pages e12274
Institution Citation Choisy, S. C., Kim, S., Hancox, J. C., Jones, S. A., & James, A. F. (2015). Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats. Physiological Reports, 3(1), e12274. doi:10.14814/phy2.12274
DOI https://doi.org/10.14814/phy2.12274
Keywords Angiotensin receptor blocker; Connexin-43; Fibrosis; Gap junction
Publisher URL http://onlinelibrary.wiley.com/doi/10.14814/phy2.12274/abstract
Copyright Statement © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Additional Information Copy of article: S. C. Choisy, S. J. Kim, J. C. Hancox, S. A. Jones, A. F. James, Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats, Physiol Rep, 3 (1), 2015, e12274, doi: 10.14814/phy2.12274

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Copyright Statement
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.



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