Reduction of ventricular hypertrophy and fibrosis in spontaneously hypertensive rats by L-arginine.
The purpose of this experiment was to explore long-term L-arginine administration on ventricular hypertrophy and cardiac fibrosis in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Twenty-four rats of each strain at eight wks of age were divided into two groups--one receiving L-arginine and the other vehicle for twelve wks. Arterial pressure (AP) and heart rate were monitored. At 20 wks of age, the rats' rings of thoracic aorta were isolated to record isometric tension. The study measured left ventricular weight (LVW), body weight (BW), left ventricular (LV) contents of cGMP, and collagen volume fraction (LVCVF). Histological examination of the LV tissue determined changes in cardiomyocytes. Administration of L-arginine did not alter the AP change in SHR, but reduced the AP in WKY after six wks. Our results showed a significantly higher LVW/BW ratio and LVCVF in vehicle-treated SHR compared to levels in corresponding WKY, whereas, the LV cGMP and nitrite/nitrate measurements were higher in vehicle-treated WKY than in SHR. L-Arginine treatment decreased LVW/BW ratio and LVCVF, while increasing the levels of LV cGMP and nitrite/nitrate only in SHR, consistent with histopathological examinations that showed L-arginine prevented cardiomyocytes from thickness and hypertrophy. Our results suggested that the mechanism of reduction in ventricular hypertrophy and fibrosis following long-term L-arginine administration in SHR may stem from increased myocardial nitric oxide-cGMP signaling, independent of AP and EDV of thoracic aorta.
Chang
Huai-Ren
HR
School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
Wu
Chia Yen
CY
Hsu
Yung-Hsiang
YH
Chen
Hsing I
HI
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000517:prevention & control*; D006152:Cyclic GMP / Q000032:analysis; D004719:Endomyocardial Fibrosis / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D009569:Nitric Oxide / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP