Protective role of pinacidil against adrenaline-induced myocardium injury in guinea pig liver mitochondria

Abstract

Abstract:We investigated the role of the ATP-sensitive potassium channel opener pinacidil and blocker glibenclamide on guinea pig liver mitochondrial function, and a possible significance of pinacidil in the pharmacological treatment during myocardium dystrophy. First, a series of experiments was performed to determine the effect of pinacidil and glibenclamide on mitochondrial oxygen consumption. We found that pinacidil increased the rate of mitochondrial respiration for FAD-generated substrate (succinate oxidation), but was most effective for α-ketoglutarate oxidation with enhancement of respiratory control ratio. Oxidation of FAD-generated substrate inhibited efficiency of phosphorylation for α-ketoglutarate oxidation in pinacidil-treated animals. Glibenclamide decreased the rate of respiration with the lowest value of efficiency of phosphorylation, especially for α-ketoglutarate oxidation. A second series of experiments was performed to determine the effects of pinacidil and glibenclamide on oxidative phosphorylation during adrenaline-induced myocardium dystrophy. The increase in respiratory control ratio and efficiency of phosphorylation for α-ketoglutarate oxidation was greater than for succinate oxidation in mitochondria of pinacidil-pretreated animals during myocardium dystrophy. Inhibitory analysis with malonate suggested that endogenous succinate increased oxidation of NADH-generated substrates in mitochondria. Pinacidil is mainly involved in the adrenaline-induced alterations of mitochondrial function due to elevation of phosphorylation efficiency for α-ketoglutarate oxidation and a decreased level of lipid peroxidation.

Modulators of KATP channels in the prevention of oxidative stress and antioxidant capacity improvement in the rat heart with different resistance to hypoxia upon cobalt treatment

“…It has been speculated that the opening of these channels during ischaemia and early reperfusion would produce ADP shortening, reducing Ca 2+ influx and consequently preventing Ca 2+ overload. Our previous studies have shown that protection induced by KATP channel openers was mediated by α-ketoglutarate oxidation and inhibition of lipid peroxidation during stress conditions (27). Our results showed that pharmacological treatment with KATP channel openers induced protective effect during stress conditions and dystrophy in the liver and myocardium of rats and guinea pigs (28).…”

“…We demonstrated a statistically significant decrease in SOD and CAT activity only in the heart of LR animals after administration of Co. These two types of animals: HR and LR were previously shown to exhibit two different functional and metabolic patterns (2,27,28). They are associated with typical differences in the activity of the central nervous system and neuro-humoral regulation, stress-activating and stress-limiting systems, oxygentransporting function of the blood and the state of membranes or receptors.…”

“…The results of oxidative phosphorylation are manifested by an increased rate of respiration and decreased phosphorylation efficiency for succinate oxidation. HR to hypoxia and other stress conditions are related to acetylcholine metabolism and domination of α-ketoglutarate oxidation as opposed to LR to hypoxia that is mediated by adrenaline and succinate oxidation in mitochondria (27).…”