title: Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats.
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.
authors.affiliation: Department of Internal Medicine III, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
authors.forename: M
authors.initials: M
authors.lastname: Nakata
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: G
authors.initials: G
authors.lastname: Nomura
authors.forename: H
authors.initials: H
authors.lastname: Toshima
authors.forename: T
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: 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
chemical_list: D000199:Actins; D015335:Molecular Probes; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D009638:Norepinephrine