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Ion channel effects of pinacidil in vascular muscle
1Cardiovascular Research Laboratory, Chiles Research Institute, Providence Medical Center, Portland, Oregon.
Abstract:
Cellular investigation of the vasodilator, pinacidil, was carried out to determine the membrane mechanisms leading to vascular muscle relaxation. Patch clamp recording of whole cell currents from isolated vascular muscle cells of rat azygos vein demonstrated a significant increase in K+ currents when 1 to 50 mumol/L pinacidil was added. The increases of K+ current by pinacidil were small (number of openings increased by 2%) when the recording pipette (and intracellular solution) contained 10 mmol/L EGTA, but were relatively large (50-300% increase in number of openings) when calcium in the intracellular solution was greater than 300 mumol/L. These observations suggest that pinacidil causes vasodilatation by increasing potassium conductance, primarily or completely via the large (200pS), calcium-dependent K+ channel.