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Effects of aldosterone and angiotensin II receptor blockade on cardiac angiotensinogen and angiotensin-converting enzyme 2 expression in Dahl salt-sensitive hypertensive rats.
Am J Hypertens. 2007 Oct; 20(10):1119-24.AJ

Abstract

BACKGROUND

We previously reported that a high-sodium diet activates the local renin-angiotensin-aldosterone system (RAAS) in cardiovascular tissues of Dahl salt-sensitive hypertensive (DS) rats. Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of blood pressure (BP) and cardiac function. The effect of blockade of aldosterone or angiotensin II (Ang II) on cardiac angiotensinogen and ACE2 in DS rats is unknown.

METHODS

The BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), heart weight, endothelium-dependent relaxation (EDR), and messenger RNA (mRNA) levels of collagen III, angiotensinogen, ACE, and ACE2 in the heart were measured in DS rats and in Dahl salt-resistant (DR) rats fed high or low salt diets. The rats were treated orally with or without eplerenone (100 mg/kg/d), candesartan (10 mg/kg/d), or both drugs combined for 8 weeks.

RESULTS

A high salt diet increased BP (140%), heart/body weight (132%), and collagen III mRNA levels (146%) and decreased PRA and PAC concomitant with increased expression of cardiac angiotensinogen mRNA and decreased mRNA levels of ACE2 in DS rats. Eplerenone or candesartan significantly decreased the systolic BP from 240 +/- 5 mm Hg to 164 +/- 4 mm Hg or to 172 +/- 10 mm Hg, respectively (P < .05). Eplerenone or candesartan partially improved heart/body weight and cardiac fibrosis, improved EDR and decreased cardiac ACE and angiotensinogen mRNA levels in DS rats. Candesartan increased ACE2 mRNA levels in the heart. Combination therapy normalized BP and further improved cardiac hypertrophy, fibrosis, and EDR.

CONCLUSIONS

In DS rats, blockade of aldosterone or Ang II protects cardiac hypertrophy and fibrosis by inactivation of the local RAAS in the heart.

Authors+Show Affiliations

Division of Endocrinology and Hypertension, Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Takara-machi, Kanazawa, Japan. takeday@im2.m.kanazawa-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17903697

Citation

Takeda, Yoshiyu, et al. "Effects of Aldosterone and Angiotensin II Receptor Blockade On Cardiac Angiotensinogen and Angiotensin-converting Enzyme 2 Expression in Dahl Salt-sensitive Hypertensive Rats." American Journal of Hypertension, vol. 20, no. 10, 2007, pp. 1119-24.
Takeda Y, Zhu A, Yoneda T, et al. Effects of aldosterone and angiotensin II receptor blockade on cardiac angiotensinogen and angiotensin-converting enzyme 2 expression in Dahl salt-sensitive hypertensive rats. Am J Hypertens. 2007;20(10):1119-24.
Takeda, Y., Zhu, A., Yoneda, T., Usukura, M., Takata, H., & Yamagishi, M. (2007). Effects of aldosterone and angiotensin II receptor blockade on cardiac angiotensinogen and angiotensin-converting enzyme 2 expression in Dahl salt-sensitive hypertensive rats. American Journal of Hypertension, 20(10), 1119-24.
Takeda Y, et al. Effects of Aldosterone and Angiotensin II Receptor Blockade On Cardiac Angiotensinogen and Angiotensin-converting Enzyme 2 Expression in Dahl Salt-sensitive Hypertensive Rats. Am J Hypertens. 2007;20(10):1119-24. PubMed PMID: 17903697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of aldosterone and angiotensin II receptor blockade on cardiac angiotensinogen and angiotensin-converting enzyme 2 expression in Dahl salt-sensitive hypertensive rats. AU - Takeda,Yoshiyu, AU - Zhu,Aoshuang, AU - Yoneda,Takashi, AU - Usukura,Mikiya, AU - Takata,Hiroyuki, AU - Yamagishi,Masakazu, PY - 2007/01/22/received PY - 2007/02/13/revised PY - 2007/05/07/accepted PY - 2007/10/2/pubmed PY - 2007/12/6/medline PY - 2007/10/2/entrez SP - 1119 EP - 24 JF - American journal of hypertension JO - Am. J. Hypertens. VL - 20 IS - 10 N2 - BACKGROUND: We previously reported that a high-sodium diet activates the local renin-angiotensin-aldosterone system (RAAS) in cardiovascular tissues of Dahl salt-sensitive hypertensive (DS) rats. Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of blood pressure (BP) and cardiac function. The effect of blockade of aldosterone or angiotensin II (Ang II) on cardiac angiotensinogen and ACE2 in DS rats is unknown. METHODS: The BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), heart weight, endothelium-dependent relaxation (EDR), and messenger RNA (mRNA) levels of collagen III, angiotensinogen, ACE, and ACE2 in the heart were measured in DS rats and in Dahl salt-resistant (DR) rats fed high or low salt diets. The rats were treated orally with or without eplerenone (100 mg/kg/d), candesartan (10 mg/kg/d), or both drugs combined for 8 weeks. RESULTS: A high salt diet increased BP (140%), heart/body weight (132%), and collagen III mRNA levels (146%) and decreased PRA and PAC concomitant with increased expression of cardiac angiotensinogen mRNA and decreased mRNA levels of ACE2 in DS rats. Eplerenone or candesartan significantly decreased the systolic BP from 240 +/- 5 mm Hg to 164 +/- 4 mm Hg or to 172 +/- 10 mm Hg, respectively (P < .05). Eplerenone or candesartan partially improved heart/body weight and cardiac fibrosis, improved EDR and decreased cardiac ACE and angiotensinogen mRNA levels in DS rats. Candesartan increased ACE2 mRNA levels in the heart. Combination therapy normalized BP and further improved cardiac hypertrophy, fibrosis, and EDR. CONCLUSIONS: In DS rats, blockade of aldosterone or Ang II protects cardiac hypertrophy and fibrosis by inactivation of the local RAAS in the heart. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/17903697/Effects_of_aldosterone_and_angiotensin_II_receptor_blockade_on_cardiac_angiotensinogen_and_angiotensin_converting_enzyme_2_expression_in_Dahl_salt_sensitive_hypertensive_rats_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1016/j.amjhyper.2007.05.008 DB - PRIME DP - Unbound Medicine ER -