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- Title
Endothelin Antagonism reverses Upregulated Renin-Angiotensin System in the hypertrophied Heart of Stroke Prone Spontaneously Hypertensive Rat (SHR-SP), not in SHR.
- Authors
Jesmin, Subrina; Mowa, Chishimba; Thompson, Morgan; Zaedi, Sohel; Miyauchi, Takashi
- Abstract
It is not known whether endothelin (ET)-1 affects the production of angiotensin II (AII) in the heart. We hypothesized that ET-1 may act upstream of renin-angiotensin system (RAS) in hypertrophied heart and tested the hypothesis by investigating the effects of ET blockade on the expression of various components of RAS, including AII in the heart of stroke prone spontaneously hypertensive rats (SHR-SP). SHR-SP were treated for 3 months with SB209670 (ET-A/-B dual receptor antagonist), or saline (vehicle) starting from the prehypertensive stage (6 weeks old). Peptide levels of AII (15-fold higher), and renin, angiotensinogen, angiotensin converting enzyme (ACE) and AII type 1 receptor (AT1R) were significantly upregulated in control SHR-SP, but reversed by long-term ET antagonism: AII type 2 receptor (AT2R) was down-regulated by about 30% in vehicle-treated SHR-SP, and was reversed by ET blockade, including the higher plasma activity of renin and ACE, and plasma levels of AII. The Chymase system was upregulated by 60% in control SHR-SP, and was reversed by ET blockade. Cardiac hypertrophy and myocardial fibrosis at histological level in SHR-SP was ameliorated by ET antagonism, and left ventricular hypertrophy, as revealed by echocardiography in SHR-SP, was also suppressed by ET blockade. These findings indicate that ET antagonism suppressed upregulated RAS in SHR-SP heart, independent of blood pressure. Furthermore, it is suggested that the ET system may act on the upstream of RAS in the heart, and that ET has some regulatory mechanisms on cardiac RAS in SHR-SP, not in SHR.
- Subjects
ENDOTHELINS; ANGIOTENSIN II; RENIN-angiotensin system; CARDIAC hypertrophy; ANGIOTENSIN converting enzyme; LABORATORY rats
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA761
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a761-c