Delayed rectifier potassium channels contribute to the depressed pulmonary artery contractility in pneumonia.
We investigated the role of K(+) channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonas pneumonia. Contractility of PA rings from the lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-response curves to the contractile agonists KCl, phenylephrine, or PGF(2 alpha) on PA rings before and after treatment with K(+) channel blockers. In rings from pneumonia rats, paxilline (10 microM), tetraethylammonium (2 mM) (blockers of large-conductance Ca(2+)-activated K(+) channels), and glybenclamide (ATP-sensitive K(+) channel blocker, 80 microM) had no significant effect on the attenuated contractile responses to KCl, phenylephrine, and PGF(2 alpha). However, 4-aminopyridine (2 mM), a blocker of voltage-gated K(+) channels (delayed rectifier K(+) channel) reversed this depressed contractility. Therefore, large-conductance Ca(2+)-activated K(+) and ATP-sensitive K(+) channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a voltage-gated K(+) channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative therapies for the pulmonary vascular abnormalities associated with this disease.
Yaghi
Asma
A
AC Burton Vascular Biology Laboratory, Division of Respiratory Medicine, London Health Sciences Centre, London, Ontario, Canada N6A 4G5.
Mehta
Sanjay
S
McCormack
David G
DG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D011014:Pneumonia / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
D051668:Delayed Rectifier Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D000255:Adenosine Triphosphate