The Role of Oxygen-Derived Free Radicals in Augmented Relaxations to Levcromakalim in the Aorta From Hypertensive Rats

Abstract

Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K⁺ channels, indicating that oxygen-derived free radicals may activate these channels. Levels of free radicals are increased throughout the arterial wall in animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive K⁺ channels may be augmented in chronic hypertension. The present study was designed to determine whether relaxations to an ATP-sensitive K⁺ channel opener, levcromakalim, are increased in the aorta from spontaneously hypertensive rats (SHR) and whether free radical scavengers reduce these relaxations. Rings of aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR were suspended for isometric force recording. Relaxations to levcromakalim (10^-8 to 10^-5 M), which are abolished by glibenclamide (10^-5 M), were augmented in the aorta from SHR, compared to those in the aorta from WKY. In the aorta from SHR, catalase (1200 U/ml), but neither superoxide dismutase (150 U/ml) nor deferoxamine (10^-4 M), reduced relaxations to levcromakalim, whereas in the aorta from WKY, the free radical scavengers did not affect these relaxations. These results suggest that in chronic hypertension, vasorelaxation to an ATP-sensitive K⁺ channel opener is augmented and that hydrogen peroxide produced in smooth muscle cells may partly contribute to these relaxations.