Nicorandil, a potent adenosine triphosphate–sensitive potassium-channel opener, ameliorates lung allograft reperfusion injury

Yamashita, Motohiro; Schmid, Ralph A.; Fujino, S; Cooper, Joel D.; Patterson, G. Alexander

doi:10.1016/s0022-5223(96)70145-9

Cited by 16 publications

(11 citation statements)

References 29 publications

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“…This result indicates that K ATP activation might stimulate Na ϩ transport in the lung, since it is the main mechanism involved in alveolar liquid clearance (4). K ATP channel openers, with a well-known protective effect against ischemiareperfusion injury in the heart, have also been shown to exert a beneficial action in the lungs (24,34,56).…”

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confidence: 98%

Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells

Leroy

Dagenais²,

Berthiaume³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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K(+) channels play a crucial role in epithelia by repolarizing cells and maintaining electrochemical gradient for Na(+) absorption and Cl(-) secretion. In the airway epithelium, the most frequently studied K(+) channels are KvLQT1 and K(Ca). A functional role for K(ATP) channels has been also suggested in the lung, where K(ATP) channel openers activate alveolar clearance and attenuate ischemia-reperfusion injury. However, the molecular identity of this channel is unknown in airway and alveolar epithelial cells (AEC). We adopted an RT-PCR strategy to identify, in AEC, cDNA transcripts for Kir channels (Kir6.1 or 6.2) and sulfonylurea receptors (SUR1, 2A, or 2B) forming K(ATP) channels. Only Kir6.1 and SUR2B were detected in freshly isolated and cultured alveolar cells. To determine the physiological role of K(+) channels in the transepithelial transport of alveolar monolayers, we studied the effect, on total short-circuit currents (I(sc)), of basolateral application of glibenclamide, an inhibitor of K(ATP) channels, as well as clofilium, charybdotoxin, clotrimazole, and iberiotoxin, inhibitors of KvLQT1 and K(Ca) channels, respectively. Interestingly, activity of the three types of K(+) channels was detected, since all tested inhibitors decreased I(sc). Furthermore, these K(+) channel inhibitors reduced amiloride-sensitive Na(+) currents (mediated by ENaC) and completely abolished stimulation of Cl(-) currents by forskolin. Conversely, pinacidil, an activator of K(ATP) channels, increased Na(+) and Cl(-) transepithelial transport by 33-35%. These results suggest the presence, in AEC, of a K(ATP) channel, formed from Kir6.1 and SUR2B subunits, which plays a physiological role, with KvLQT1 and K(Ca) channels, in Na(+) and Cl(-) transepithelial transport.

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confidence: 98%

Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells

Leroy

Dagenais²,

Berthiaume³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…ATP-dependent potassium channels can be influenced by the intracellular ATP concentration, but also by endothelial mediators like prostacyclin and endothelin [14, 17, 18]. The opening of these channels has been suggested to prevent and reverse the ischaemia-reperfusion-induced increase in microvascular permeability seen in the lung [19, 20], indicating that the ATP-dependent potassium channels in the endothelial cells might be of importance in the regulation of vascular permeability.…”

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confidence: 99%

Prostacyclin Reduces Microvascular Fluid Conductivity in Cat Skeletal Muscle through Opening of ATP-Dependent Potassium Channels

1999

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Prostacyclin is suggested to reduce microvascular permeability, but the cellular mechanisms mediating this response in the microvascular endothelial cells are still unknown. Considering that prostacyclin relaxes vascular smooth muscle cells via opening of ATP-dependent potassium channels, and opening of ATP-dependent potassium channels in the endothelial cells is suggested to influence microvascular permeability, this study was designed to test (1) if ATP-dependent potassium channels are involved in the regulation of microvascular hydraulic permeability, (2) if the permeability-reducing effect of prostacyclin is mediated through opening of ATP-dependent potassium channels, and (3) if cAMP is involved in this process. An autoperfused cat calf hindlimb was used as experimental model, and microvascular hydraulic permeability (conductivity) was estimated by a capillary filtration coefficient (CFC) technique. The potassium channel opener PCO-400 (0.5 μg·min^–1 per 100 g muscle, intra-arterially), prostacyclin (1 ng·min^–1 per kg body weight, intravenously) and the cAMP analogue dibutyryl-cAMP (24 μg·min^–1 per 100 g muscle, intra-arterially), decreased CFC to 77, 72 and 69% compared to control, respectively (p < 0.01). The decrease in CFC obtained by these substances was completely restituted after the start of a simultaneous infusion of the ATP-dependent potassium channel blocker glibenclamide (6 μg·min^–1 per 100 g muscle, intra-arterially; p < 0.01). Infusion of glibenclamide alone increased CFC to 107% of control (p < 0.05). In conclusion, the ATP-dependent potassium channels contribute to the regulation of microvascular hydraulic conductivity, and the prostacyclin permeability-reducing effect may act through this mechanism via increase in intracellular cAMP.

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“…However, there have been only a few studies on the effect of KATP openers on lung reperfusion injury (13,14). Moreover, there has been no study concerning the effectiveness of pinacidil (a relatively pure KATP opener) in lung preservation.…”

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confidence: 99%

“…However, in clinical lung transplantation, the donor lung is flushed and preserved with cold solution and perfused with blood when reperfused; therefore, the experimental setting of cold ischemia, which was used in our study, would be more practical for lung preservation. Yamashita and associates (14) reported the effect of nicorandil on reperfusion injury after cold ischemia in a canine lung transplantation model. However, nicorandil is a hybrid between a nicotinamide nitrate and a KATP opener, and the nitric oxide donor effect of nicorandil cannot be ignored.…”

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confidence: 99%

Effect of Adenosine Triphosphate–Sensitive Potassium Channel Openers on Lung Preservation

Fukuse

Hirata²,

Omasa³

et al. 2002

Am J Respir Crit Care Med

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ATP-sensitive potassium channel (KATP) openers have been proven to be involved in ischemic preconditioning, which protects ischemic tissue. However, the effect of KATP openers on ischemia-reperfusion injury of the lungs remains unknown. We investigated whether a KATP opener, pinacidil, can attenuate ischemia-reperfusion injury using an ex vivo rat lung model. Heart-lung blocks were flushed and preserved with phosphate-buffered saline (control group) or with one of the solutions containing pinacidil (pinacidil group) or pinacidil + glibenclamide (a KATP blocker) (glibenclamide group). The control and glibenclamide groups showed significantly higher values with respect to shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure than the pinacidil group. The concentrations of total adenine nucleotides and ATP in the lung after reperfusion became significantly lower in the control and glibenclamide groups than in the fresh group. Lipid peroxidation of the lungs increased significantly in the control and glibenclamide groups after reperfusion. State 3 mitochondrial respiration and State 3/4 ratios of mitochondrial respiration were significantly decreased in the lungs of the control and glibenclamide groups. These findings suggested that KATP openers would maintain the mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia-reperfusion injury.

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Nicorandil, a potent adenosine triphosphate–sensitive potassium-channel opener, ameliorates lung allograft reperfusion injury

Cited by 16 publications

References 29 publications

Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells

Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells

Prostacyclin Reduces Microvascular Fluid Conductivity in Cat Skeletal Muscle through Opening of ATP-Dependent Potassium Channels

Effect of Adenosine Triphosphate–Sensitive Potassium Channel Openers on Lung Preservation

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Nicorandil, a potent adenosine triphosphate–sensitive potassium-channel opener, ameliorates lung allograft reperfusion injury

Cited by 16 publications

References 29 publications

Molecular identity and function in transepithelial transport of KATP channels in alveolar epithelial cells

Molecular identity and function in transepithelial transport of KATP channels in alveolar epithelial cells

Prostacyclin Reduces Microvascular Fluid Conductivity in Cat Skeletal Muscle through Opening of ATP-Dependent Potassium Channels

Effect of Adenosine Triphosphate–Sensitive Potassium Channel Openers on Lung Preservation

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Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells

Molecular identity and function in transepithelial transport of K_ATP channels in alveolar epithelial cells