Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats.
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.
Matsuoka
H
H
Department of Internal Medicine III, Kurume University School of Medicine, Fukuoka, Japan.
Nakata
M
M
Kohno
K
K
Koga
Y
Y
Nomura
G
G
Toshima
H
H
Imaizumi
T
T
D000199:Actins / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology*; D006152:Cyclic GMP / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D013997:Time Factors
D000199:Actins; D015335:Molecular Probes; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D009638:Norepinephrine