title: Activation of ATP-sensitive potassium channels by nicorandil is preserved in aged vascular smooth muscle cells in rats.
abstract: Nicorandil, an ATP-sensitive potassium (KATP) channel opener having the properties of a nitrate, causes vasodilation, particularly of coronary arteries, and has been reported to reduce the frequency of perioperative cardiac events. We previously demonstrated that isoflurane could activate vascular KATP channels through an intracellular signaling pathway, but that this isoflurane-induced channel opening is suppressed by aging. Here, we investigated whether advanced age modifies nicorandil-induced activation of vascular KATP channels. We used a cell-attached patch-clamp configuration to test the effects of nicorandil on KATP channel activity in vascular smooth muscle cells (VSMCs) obtained from 12- to 15-week-old (adult) and 24- to 25-month-old (aged) male Wistar rats. Bath application of nicorandil (0.1-100 μM) activated KATP channels to a level similar to that observed in VSMCs from the arteries of both adult and aged rats. Furthermore, concomitant bath application of nicorandil in the aged group dose-dependently ameliorated the age-related reduction in isoflurane-induced vascular KATP channel activation. Our findings indicate that nicorandil could be used effectively in elderly patients to directly activate vascular KATP channels during the perioperative period.
authors: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan.
authors: Fumimoto
authors: F
authors: Yamazaki
authors: Haidong
authors: H
authors: Chi
authors: Satoru
authors: S
authors: Eguchi
authors: Takashi
authors: T
authors: Kawano
mesh_terms: D000367:Age Factors; D000818:Animals; D007530:Isoflurane / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D054086:KATP Channels; D014665:Vasodilator Agents; D020108:Nicorandil; D007530:Isoflurane