Effects of charybdotoxin on responses to nitrosovasodilators and hypoxia in the rat lung.
This study investigated the effects of the Ca2+-sensitive K+ channel antagonist charybdotoxin on responses to the nitrosovasodilators nitroglycerin and sodium nitroprusside and on pulmonary pressor responses to ventilatory hypoxia in the isolated blood-perfused rat lung. Injections of nitroglycerin and sodium nitroprusside induced dose-related decreases in pulmonary arterial perfusion pressure when tone was increased with U-46619, whereas ventilatory hypoxia (3% O2-5% CO2-balance N2) increased pulmonary arterial perfusion pressure in a reproducible manner. After administration of charybdotoxin, the pressor response to ventilatory hypoxia was significantly increased, whereas charybdotoxin significantly decreased vasodilator responses to nitroglycerin and sodium nitroprusside but had no effect on the vasodilator responses to albuterol or to isoproterenol when tone was increased with U-46619. The results of the present study show that charybdotoxin enhances the pressor response to ventilatory hypoxia and significantly decreases responses to nitric oxide-donating vasodilator agonists in a selective manner. These data suggest that the response to ventilatory hypoxia is modulated by alterations in Ca2+-sensitive K+ channel activity and suggest that vasodilator responses to the nitric oxide donors nitroglycerin and sodium nitroprusside are dependent on the opening of large-conductance Ca2+-sensitive K+ channels in the pulmonary vascular bed of the rat.
Nossaman
B D
BD
Department of Anesthesiology, Tulane University Medical School, New Orleans, Louisiana 70112-2699, USA.
Kaye
A D
AD
Feng
C J
CJ
Kadowitz
P J
PJ
D000280:Administration, Inhalation; D000818:Animals; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology*; D005740:Gases / Q000008:administration & dosage; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D005740:Gases; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D018999:Charybdotoxin; D009599:Nitroprusside; D005996:Nitroglycerin; D002118:Calcium