Mocanu, M.M.;
Maddock, H.L.;
Baxter, G.F.;
Lawrence, C.L.;
Standen, N.B.;
Yellon, D.M.;
(2001)
Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.
Circulation
, 103
(25)
pp. 3111-3116.
![[thumbnail of 7799.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
7799.pdf Download (502kB) |
Abstract
Background: The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial KATP channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic KATP channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial KATP channels. Methods and results: Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2x 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 µmol/L Diaz, (4) 10 µmol/L Glim, (5) 10 µmol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5±1% vs 43.7±3% in control, P<0.01) as did Diaz (22.2±4.7%, P<0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5±3% in IP+Glim, 22.3±3% in Diaz+Glim; P<0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 µmol/L) blocked sarcolemmal KATP currents. However, in isolated cardiac mitochondria, Glim (10 µmol/L) failed to block the effects of KATP opening by GTP, in contrast to the blockade caused by Glib. Conclusions: Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial KATP channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease.
| Type: | Article |
|---|---|
| Title: | Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide |
| Identifier: | PMID: 11425777 |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://circ.ahajournals.org/cgi/content/full/103/2... |
| Language: | English |
| Additional information: | Basic science reports |
| Keywords: | Potassium, myocardial infarction, diabetes mellitus, ion channels |
| UCL classification: | |
| URI: | https://discovery.ucl.ac.uk/id/eprint/7799 |
Archive Staff Only
 |
View Item |
