Effect of pinacidil on rat ventricular myocytes during transient hypoxia and reperfusion.

Abstract

The aim of this study was to evaluate the cardioprotective effect of pinacidil postconditioning on rat hearts with transient hypoxia and reperfusion. An acute myocardial anoxia-reperfusion rat model was created by ligating coronary arteries for 10 min and subsequent reperfusion for 60 min. Twenty-four rats in 4 groups received different treatments: normal hearts as control (N = 6), anoxia-reperfusion (A/R) only (N = 6), pinacidil postconditioning (N = 6), and pinacidil plus adenosine triphosphate-sensitive potassium channel inhibitors (glibenclamide) (N = 6). The kinetic parameters and electrophysiological properties, including early apoptosis protein expression changes of Bax, Bcl-2, and FN were examined using the isolated perfusion and patch-clamp technique and immunohistochemistry. The left ventricular systolic pressure and maximum -dp/dt in A/R groups were significantly higher than those in the control group (P < 0.05). The left ventricular developing pressure, maximum +dp/dt, and heart rate in the A/R group were slightly decreased. The pinacidil-postconditioned group has better cardiac function recovery after ischemia/reperfusion than the A/R group (P < 0.01). In addition, using the patch-clamp technique, the mean open time and conductance values are significantly higher in the pinacidil postconditioning group, compared with those in the A/R group. The expression of apoptosis proteins (Bax, FN) increased during A/R, while Bcl-2 protein expression decreased. A significant difference was found in the pinacidil treatment group relative to the A/R group. Pinacidil postconditioning can exert cardioprotective effects on A/R-injured rat hearts, which may indicate a potential application of pinacidil postconditioning to protect A/R-injured hearts.

• Authors: X Y Dong, F Zhu
• Journal: Genetics and molecular research : GMR (Genet Mol Res) Vol. 13 Issue 4 Pg. 8197-208 (Oct 08 2014) ISSN: 1676-5680 [Electronic] Brazil
• PMID: 25299204 (Publication Type: Journal Article)

Chemical References

• Potassium Channels
• Vasodilator Agents
• Pinacidil

Topics

• Animals
• Apoptosis
• Heart Ventricles (drug effects, metabolism)
• Hypoxia
• Male
• Models, Animal
• Myocardial Reperfusion
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism)
• Pinacidil (administration & dosage, pharmacology)
• Potassium Channels (metabolism)
• Rats
• Vasodilator Agents (pharmacology)
• Ventricular Function, Left