In vitro responses of lung arteries to acute hypoxia after NO synthase blockade or chronic hypoxia.
Responses to hypoxia of lung arteries (200-350 microns) from control (C) and chronically hypoxic (CH) rats were compared in a myograph before and after blockade of NO synthase with NG-nitro-L-arginine methyl ester (L-NAME). After precontraction with prostaglandin F2 alpha (PGF2 alpha), hypoxia caused a four-phase tension change: brief dilation, transient contraction, prolonged dilation, and slow contraction (we studied the first three phases). In CH rats, the first dilation and first contraction were significantly reduced. After L-NAME, the first dilation was reduced in C rats and abolished in CH rats; thus the first phase is attributable to NO release and is affected by chronic hypoxia. The first contractile phase was significantly reduced by L-NAME in C but not in CH rats, where it was small. Thus NO synthase inhibition inhibits hypoxic constriction in isolated vessels, whereas it enhances hypoxic constriction in perfused lungs. The third dilator phase was unaffected by chronic hypoxia; it was increased after L-NAME in CH rats. Thus, in vitro, responses to hypoxia are complex; there is a balance between two dilator and two constrictor processes.
Teng
G Q
GQ
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Barer
G R
GR
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010120:Oxytocics / Q000494:pharmacology; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D010120:Oxytocics; D001120:Arginine; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester