Initiation of remote microvascular preconditioning requires K(ATP) channel activity

Area of Science:

• Physiology
• Vascular Biology
• Cellular Signaling

Background:

• Remote microvascular preconditioning (RMP) alters upstream arteriole responses to downstream agonist exposure.
• Mitochondrial ATP-sensitive K+ (K(ATP)) channels are hypothesized to mediate RMP.

Purpose of the Study:

• To investigate the role of mitochondrial K(ATP) channels in mediating RMP.
• To determine the signaling pathway involved in RMP.

Main Methods:

• Studied arteriolar diameter in hamster cheek pouch microcirculation.
• Applied various agonists (pinacidil, diazoxide, sodium nitroprusside, bradykinin) and inhibitors (5-hydroxydecanoate, N-omega-nitro-L-arginine) via micropipette.
• Assessed vasoactive responses to L-arginine.

Main Results:

• Pinacidil, diazoxide, sodium nitroprusside, and bradykinin all stimulated RMP.
• 5-Hydroxydecanoate blocked RMP induced by pinacidil, diazoxide, and sodium nitroprusside.
• N-omega-nitro-L-arginine blocked RMP during sodium nitroprusside stimulation but not diazoxide stimulation.

Conclusions:

• Mitochondrial K(ATP) channels are essential for RMP.
• RMP requires mitochondrial K(ATP) channel activity subsequent to nitric oxide donor stimulation.