Effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary vasoconstriction.
This study investigated the effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary vasoconstriction induced in isolated rat lung perfused at constant flow. In order to evaluate the mechanism of the hypoxic vasoconstriction we also studied the effects of an inhibitor of the endothelium-derived relaxing factor (EDRF), NG-nitro-L-arginine methyl ester (100 microM), an inhibitor of the guanylate cyclase, methylene blue (30 microM), two K+ channel blockers, glibenclamide (1 microM) and tetraethylammonium (20 mM). In normoxia, NG-nitro-L-arginine methyl ester, methylene blue, glibenclamide or tetraethylammonium did not enhance significantly the baseline perfusion pressure, suggesting that neither EDRF nor K+ channels are involved in the modulation of the low basal pulmonary vascular tone. In hypoxia, aprikalim and pinacidil (0.03-3 microM) induced a concentration-dependent decrease of pulmonary pressure, exhibiting their spasmolytic effects in acute hypoxia. The hypoxic pressure response was significantly increased by NG-nitro-L-arginine methyl ester, methylene blue and tetraethylammonium, but not by glibenclamide suggesting that EDRF and K+ channels other than ATP-sensitive K+ channels are involved in the modulation of the hypoxic pressure response. The spasmolytic effects of aprikalim and pinacidil (1 microM) were not modified by NG-nitro-L-arginine methyl ester, but were partially reduced by tetraethylammonium and completely abolished by glibenclamide, suggesting that these effects are mainly but not exclusively mediated through ATP-sensitive K+ channel opening.
Dumas
J P
JP
Laboratoire de Physiologie, Faculté de Médecine, Dijon, France.
Dumas
M
M
Sgro
C
C
Advenier
C
C
Giudicelli
J F
JF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006146:Guanidines / Q000627:therapeutic use*; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010847:Picolines / Q000627:therapeutic use*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D006146:Guanidines; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D014665:Vasodilator Agents; D009569:Nitric Oxide; C061043:aprikalim; D020110:Pinacidil; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester