&ITN&IT-Acetylcysteine-induced vasodilatation is modulated by K-ATP channels, Na+/K+-ATPase activity and intracellular calcium concentration: An &ITin vitro &ITstudy

Background: In this study, we aimed to investigate the role of ATP-sensitive potassium (K-ATP) channel, Na+/K+-ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. Methods: Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2 mM NAC, 5 mM NAC, and 10 mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na+/K+-ATPase activity. In the cultured thoracic aorta cells, we measured the currents of K-ATP channel, the concentration of intracellular calcium and mRNA expression level of K-ATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). Results: The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na+/K+-ATPase activity also significantly decreased in NAC groups. Outward K-ATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxation rate was significantly associated with K-ATP current, intracellular calcium concentration, Na+/K+-ATPase activity and mRNA expression level of ABCC8 subunit. Conclusion: Our findings suggest that NAC relaxes vascular smooth muscle cells through a direct effect on K(ATP )channels, by increasing outward K+ flux, partly by increasing mRNA expression of K-ATP subunit ABCC8, by decreasing in intracellular calcium and by decreasing in Na+/K+-ATPase activity. (C) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.