L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats.
We investigated whether loss of endothelial-derived relaxing factor (EDRF) activity in the pulmonary vessels of chronically hypoxic rats could be restored by pretreatment with L-arginine. We measured vasodilation to acetylcholine (ACh), calcium ionophore A23187, or linsidomine (Sin-1) under conditions of increased vascular tone induced by U-46619 (50 pmol/min), as well as vasoconstriction to endothelin-1 (ET) in isolated lungs pretreated with meclofenamate (3 microM). In lungs from normoxic (N) rats, in vitro L- or D-arginine (10(-3) M) did not alter vasodilation to the endothelium-dependent agents ACh (10(-9)-10(-6) M) and A23187 (10(-9)-10(-7) M), but NG-monomethyl-L-arginine (10(-3) M) completely abolished it. In lungs from rats exposed to 3 wk of hypoxia (H), vasodilation to ACh or A23187 was fully restored after in vitro L-arginine (10(-3) M) or N alpha-benzoyl-L-arginine (5 x 10(-5) M) but remained abolished after D-arginine, L-citrulline, L-ornithine, or L-argininosuccinic acid. In vivo pretreatment of H rats with L-arginine (300 mg/kg iv) 30 min before isolating the lung also restored vasodilation to A23187. Vasodilation to the endothelium-independent agent Sin-1 was similar in both groups of lungs and was not altered by in vitro L-arginine. L-arginine attenuated the increased pressor response to ET (300 pmol) of H rat lungs but had no effect in N rats. Our results demonstrate that loss of EDRF activity associated with hypoxic pulmonary hypertension may be reversed by supplying L-arginine.
Eddahibi
S
S
Département de Physiologie, Institut National de la Santé et de la Recherche Médicale, U 296, Hôpital Henri Mondor, Créteil, France.
Adnot
S
S
Carville
C
C
Blouquit
Y
Y
Raffestin
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002908:Chronic Disease; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D000001:Calcimycin; D001120:Arginine; D000109:Acetylcholine