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Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats
H Matsuoka1, M Nakata, K Kohno
1Department of Internal Medicine III, Kurume University School of Medicine, Fukuoka, Japan.
Insights
L-arginine supplementation reduced cardiac hypertrophy in spontaneously hypertensive rats by improving the nitric oxide pathway. This treatment enhanced heart function and cGMP levels without affecting blood pressure.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Pharmacology
Background:
- Nitric oxide (NO) plays a crucial role in regulating vascular and cardiac function.
- Spontaneously hypertensive rats (SHR) exhibit abnormalities in the L-arginine-nitric oxide pathway.
- Cardiac hypertrophy is associated with impaired NO signaling.
Purpose of the Study:
- To investigate the in vivo effects of L-arginine supplementation on cardiac hypertrophy in SHR.
- To determine if L-arginine impacts cardiac function independently of blood pressure.
- To explore the influence of L-arginine on the L-arginine-nitric oxide axis in the heart.
Main Methods:
- Administration of L-arginine or vehicle to SHR and Wistar-Kyoto rats (WKY) for 12 weeks.
- Assessment of heart/body weight ratio and skeletal alpha-actin mRNA expression.
- Measurement of cardiac cyclic guanosine monophosphate (cGMP) and nitrate/nitrite levels.
Main Results:
- L-arginine treatment significantly reduced the heart/body weight ratio in SHR but not WKY.
- Skeletal alpha-actin mRNA expression was attenuated in L-arginine-treated SHR.
- Cardiac cGMP and nitrate/nitrite levels increased in L-arginine-treated SHR, indicating enhanced NO production.
Conclusions:
- Chronic L-arginine administration attenuates cardiac hypertrophy in SHR independent of arterial pressure.
- The L-arginine-nitric oxide axis is a potential therapeutic target for cardiac hypertrophy.
- Abnormalities in the cardiac L-arginine-nitric oxide pathway contribute to cardiac hypertrophy pathogenesis in SHR.
Abstract:
Nitric oxide inhibits proliferation and migration of vascular smooth muscle cells and contractility of cardiomyocytes in vitro. In spontaneously hypertensive rats (SHR), evidence suggests intrinsic abnormalities of the L-arginine-nitric oxide axis, such as low cGMP-dependent protein kinase in the heart and abnormal L-arginine metabolism. To investigate the in vivo effect of L-arginine on cardiac hypertrophy, 30 SHR and 30 Wistar-Kyoto rats (WKY) were randomly grouped to receive L-arginine (7.5 g/L in drinking water) or vehicle for 12 weeks. L-Arginine treatment did not affect body weight or arterial pressure in either strain. In vehicle-treated animals, the heart/body weight ratio was significantly higher in SHR than in WKY (P < .01). L-Arginine treatment decreased the heart/body weight ratio in SHR (P < .05) but did not affect it in WKY. Expression of skeletal alpha-actin mRNA, known to be expressed in the hypertrophied myocardium, was attenuated in L-arginine-treated SHR compared with vehicle-treated SHR. Cardiac cGMP content and nitrate/nitrite content were less in SHR than WKY. L-Arginine treatment increased these levels only in SHR, suggesting enhanced nitric oxide production. Thus, chronic L-arginine administration attenuated cardiac hypertrophy independently of blood pressure and increased myocardial content of cGMP and nitrate/nitrite. Our results suggest that abnormality of the cardiac L-arginine-nitric oxide axis may play an important role in the pathogenesis of cardiac hypertrophy in SHR.