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 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.
Department of Anesthesia, Japanese Red Cross Society Wakayama Medical Center. hkinoshi@pd5.so-net.ne.jp
H
H
Kinoshita
T
T
Kakutani
H
H
Iranami
Y
Y
Hatano
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D005905:Glyburide