Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta.
The involvement of the superoxide anion in endothelium-dependent relaxation (EDR) was examined in noradrenaline-contracted aortic smooth muscle preparations isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acetylcholine (ACh, 10(-9)-10(-5) M) induced EDR in both WKY and SHRSP preparations in a concentration-dependent manner, but with a significantly smaller amplitude in those from SHRSP than in those from WKY. The ACh-induced EDR was inhibited by N(omega)-nitro-L-arginine (L-NOARG), in a concentration-dependent manner, both in WKY and SHRSP. The EDR produced in WKY in the presence of 3 x 10(-6) M L-NOARG was similar in magnitude to that produced in SHRSP in the absence of L-NOARG. Superoxide dismutase (SOD, 300 units/ml) increased the amplitude of EDR in SHRSP but not in WKY, with no alteration of the threshold or of the maximal amplitude. The maximal amplitude of EDR produced in SHRSP in the presence of SOD was still smaller than that in WKY. In WKY, a possible involvement of superoxide in the EDR was examined in aortae whose EDR was partially inhibited by treatment with a subthreshold concentration (3 x 10 (-6) M) of L-NOARG. In the L-NOARG-conditioned aorta, the reduced EDR was partially but significantly recovered by SOD. These results suggest that the impaired EDR in aortae of SHRSP may be causally related to a higher production of superoxide. The L-NOARG-induced inhibition of EDR in WKY may be produced, in part, by the reduction of effective NO due to its destruction by superoxide.
Sekiguchi
Fumiko
F
School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan. fumiko@phar.kindai.ac.jp
Yanamoto
Aiko
A
Sunano
Satoru
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure; D001835:Body Weight; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000109:Acetylcholine