Influence of N omega-nitro-L-arginine methyl ester, LY83583, glybenclamide and L158809 on pulmonary circulation.
The effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of soluble guanylate cyclase; glybenclamide, a ATP-sensitive K+ channel blocking agent; and 5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl)-[1,1']-biphenyl-4- yl]methyl]-3H-imidazo[4,5-b]pyridine (L158809), an angiotensin II type I receptor antagonist, on the response to ventilatory hypoxia were investigated in the isolated blood-perfused rat lung. Under conditions of controlled pulmonary blood flow, and constant left atrial pressure, injections of glybenclamide into the pulmonary arterial perfusion circuit significantly increased baseline pulmonary arterial perfusion pressure, whereas administration of N omega-nitro-L-arginine methyl ester produced smaller increases in baseline tone. Ventilatory hypoxia (3% O2-5% CO2-92% N2) significantly increased pulmonary arterial perfusion pressure and the response was reproducible with respect to time. Following administration of N omega-nitro-L-arginine methyl ester or LY83583, the response to hypoxia was significantly increased, whereas the response to hypoxia was not changed by glybenclamide or atropine. N omega-Nitro-L-arginine methyl ester also significantly enhanced pressor responses to angiotensin II, but had no effect on the pressor response to serotonin. When pulmonary vascular tone was increased with hypoxia, vasodilator responses to acetylcholine were inhibited by N omega-nitro-L-arginine methyl ester and vasodilator responses to levcromakalim were reduced by glybenclamide. In addition, L158809 did not alter the pressor response to hypoxia, whereas responses to angiotensin II were reduced in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Feng
C J
CJ
Department of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112-2699.
Cheng
D Y
DY
Kaye
A D
AD
Kadowitz
P J
PJ
Nossaman
B D
BD
D000634:Aminoquinolines / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D000634:Aminoquinolines; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013777:Tetrazoles; D009569:Nitric Oxide; C070967:L 158809; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester