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: Roger J Legtenberg, Ralph J Houston, Paul Smits, Berend Oeseburg
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 530 Pg. 519-26 ( 2003) ISSN: 0065-2598 [Print] United States
• PMID: 14562747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• Pinacidil
• Glyburide

Topics

• Animals
• Glyburide (pharmacology)
• Heart (drug effects)
• In Vitro Techniques
• Ion Channel Gating (drug effects)
• Male
• Myocardial Ischemia (prevention & control)
• Pinacidil (pharmacology)
• Potassium Channels (drug effects, physiology)
• Rats
• Rats, Wistar