Faculty Collaboration Database

Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart. Am J Physiol 1997 Jun;272(6 Pt 2):H2607-15

Date

06/01/1997

Pubmed ID

9227537

DOI

10.1152/ajpheart.1997.272.6.H2607

Scopus ID

2-s2.0-33751275016 (requires institutional sign-in at Scopus site)   94 Citations

Abstract

The ATP-sensitive potassium (KATP) channel has been demonstrated to be a potential mediator of ischemic preconditioning (PC) in most species, with the exception of the rat. This conclusion is based on the failure of the KATP channel antagonist glibenclamide (Glib) to block PC in this species. However, previous studies did not take into consideration the kinetic properties of Glib binding to its receptor in the rat myocardium. Therefore, the purpose of the present study was to test the hypothesis that ischemic PC is mediated by the myocardial KATP channel in the rat and that blockade of PC by Glib is a time-dependent phenomenon. Barbiturate-anesthetized, open-chest male Wistar rats were subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. Infarct size (IS) as a percentage of the area at risk (AAR; IS/AAR) was determined with triphenyltetrazolium staining. PC and the KATP channel opener nicorandil (50 micrograms.kg-1.min-1 i.v.) resulted in marked reductions in IS/AAR from 53 +/- 3% to 8 +/- 1% and 17 +/- 5%, respectively (P < 0.05). Two doses of Glib (1 or 0.3 mg/kg i.v.) given 30 min before PC abolished the protective effect of PC; however, Glib (0.3 mg/kg i.v.) given 5 min before PC failed to block the effect. Glib administered 30 min before the 15-min nicorandil infusion blocked the cardioprotective effect of NC but did not block its transient hypotensive effect. These results demonstrate that the KATP channel is involved in ischemic PC in the intact rat heart and that the inhibitory effect of Glib to block PC is time dependent.

Author List

Schultz JE, Yao Z, Cavero I, Gross GJ

MESH terms used to index this publication - Major topics in bold

Animals
Antihypertensive Agents
Blood Glucose
Glyburide
Heart
Hemodynamics
Hypotension
Ischemic Preconditioning
Male
Myocardial Infarction
Niacinamide
Nicorandil
Rats
Rats, Wistar
Time Factors