The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats

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 wal l in animal models of atherosclerosis, and therefore, vasorelaxation via AT P-sensitive K+ channels may be augmented in chronic hypertension. The prese nt study was designed to determine whether relaxations to an ATP-sensitive K+ channel opener, levcromakalim, are increased in the aorta from spontaneo usly hypertensive rats (SHR) and whether free radical scavengers reduce the se relaxations. Rings of aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR were suspended for isometric force recordin g. Relaxations to levcromakalim (10(-8) to 10(-5) M), which are abolished b y 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), re duced 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+ channe l opener is augmented and that hydrogen peroxide produced in smooth muscle cells may partly contribute to these relaxations.