Hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy is unaltered by long-term oral L-arginine administration.
Nitric oxide has been shown to reduce the development of chronic hypoxic pulmonary hypertension. L-arginine is the substrate for endogenous nitric oxide synthesis. The aim of this study was to investigate whether oral L-arginine prevents the development of pulmonary vascular and right ventricular hypertrophy in adult chronic hypoxic rats. Male rats were maintained in either normoxic or hypobaric hypoxic (10% O(2)) chambers for two weeks as controls or treated with L-arginine (2 g kg(-1) day(-1) in the drinking water). Both in vehicle and L-arginine-treated rats, chronic hypoxia caused right ventricular hypertrophy, increased media to lumen ratio and increased lung weight. Contraction to the thromboxane analogue, U46619, was increased in intrapulmonary arteries, while systemic blood pressure was unaltered. Relaxations induced by the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), were increased in arteries from L-arginine-treated normoxic and hypoxic animals. In conclusion, long-term oral L-arginine administration fails to prevent development of right ventricular hypertrophy and vascular media hypertrophy in adult chronic hypoxic rats.
Laursen
Britt Elmedal
BE
Department of Pharmacology, University of Aarhus, 8000 Arhus C, Denmark. britt@farm.au.dk
Dam
Mette Y
MY
Mulvany
Michael J
MJ
Simonsen
Ulf
U
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002908:Chronic Disease; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
C110881:S-nitro-N-acetylpenicillamine; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D010396:Penicillamine; D000109:Acetylcholine; D010100:Oxygen