Preconditioning modulates pulmonary endothelial dysfunction following ischemia-reperfusion injury in the rat lung: role of potassium channels.

Abstract

Ischemic preconditioning (IP) may protect the lung from ischemia-reperfusion (I/R) injury following cardiopulmonary by-pass and lung or heart transplantation. The present study was undertaken to investigate the role of ATP-dependent potassium channels (K(ATP)) in IP in the isolated buffer-perfused rat lung (IBPR) under conditions of elevated pulmonary vasoconstrictor tone (PVT). Since pulmonary arterial perfusion flow and left atrial pressure were constant, changes in pulmonary arterial pressure (PAP) directly reflect changes in pulmonary vascular resistance (PVR). When compared to control value, the pulmonary vasodilator responses to histamine and acetylcholine (ACh) following 2 h of hypothermic ischemia were significantly attenuated, whereas the pulmonary vasodilator response to sodium nitroprusside (SNP) was not altered. IP in the form of two cycles of 5 min of ischemia and reperfusion applied prior to the two-hour interval of ischemia, prevented the decrease in the pulmonary vasodilator responses to histamine and ACh. Pretreatment with glybenclamide (GLB) or HMR-1098, but not 5-hydroxydecanoic acid (5-HD), prior to IP abolished the protective effect of IP. In contrast, GLB or 5-HD did not significantly alter the pulmonary vasodilator response to histamine without IP pretreatment. The present data demonstrate that IP prevents impairment of endothelium-dependent vasodilator responses in the rat pulmonary vascular bed. The present data further suggest that IP may alter the mediation of the pulmonary vasodilator response to histamine and thereby trigger a mechanism dependent on activation of sarcolemmal, and not mitochondrial, K(ATP) channels to preserve endothelial-dependent vasodilator responses and protect against I/R injury in the lung.

• Authors: H Burak Kandilci, Bülent Gümüşel, A Tuncay Demiryürek, Howard Lippton
• Journal: Life sciences (Life Sci) Vol. 79 Issue 23 Pg. 2172-8 (Nov 02 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16919300 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Benzamides
• Decanoic Acids
• Histamine Agents
• Hydroxy Acids
• Potassium Channels
• Vasodilator Agents
• Nitroprusside
• 5-hydroxydecanoic acid
• Histamine
• HMR 1098
• Acetylcholine
• Glyburide

Topics

• Acetylcholine (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Benzamides (pharmacology)
• Decanoic Acids (pharmacology)
• Endothelium, Vascular (metabolism)
• Glyburide (pharmacology)
• Heart Transplantation (methods)
• Histamine (pharmacology)
• Histamine Agents (pharmacology)
• Hydroxy Acids (pharmacology)
• Ischemic Preconditioning
• Lung (blood supply, metabolism)
• Lung Diseases (metabolism)
• Lung Transplantation (methods)
• Male
• Mitochondria (metabolism)
• Nitroprusside (pharmacology)
• Perfusion (methods)
• Potassium Channels (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism)
• Time Factors
• Vascular Resistance (drug effects)
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)