title: Pinacidil-induced opening, like glibenclamide-induced closure of cardiac KATP channels, protects cardiac function against ischemia in isolated, working, erythrocyte perfused rat hearts.
abstract: Glibenclamide-induced closure of ATP-dependent potassium (KATP) channels decreases coronary blood flow during normoxic and post-ischemic conditions. We have found that post-ischemic cardiac function is improved after glibenclamide treatment. Our theory was that this is a result of higher intracellular calcium concentrations due to reduction in ischemia-mediated hyperpolarization of the myocardial cell membrane. We hypothesized therefore that opening KATP channels would reduce post-ischemic function in our isolated, erythrocyte perfused, working rat heart model. During treatment with 1 or 12 mumol.L-1 pinacidil (protein unbound concentration) both before and after 12 minutes global ischemia coronary blood flow increased 2-3 fold compared with vehicle, while cardiac functional recovery post-ischemically was improved with both concentrations. Because closing and opening cardiac KATP channels both improve post-ischemic function, our calcium theory above can be discounted. The protective effect of glibenclamide may possibly be ascribed to metabolic effects such as preservation of ATP levels during ischemia.
authors.affiliation: Department of Physiology 237, University of Nijmegen, The Netherlands.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Legtenberg
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Houston
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Berend
authors.initials: B
authors.lastname: Oeseburg
mesh_terms: D000818:Animals; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; D020110:Pinacidil; D005905:Glyburide