Effect of superoxide dismutase on hemorrhagic hypotension and retransfusion-evoked middle cerebral artery endothelial dysfunction.
Middle cerebral artery rings (MCA) were prepared from control and hemorrhagic hypotension and retransfusion-subjected (HHR) cats, with or without superoxide dismutase (SOD) treatment. Two-mm-long MCA segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. HHR was produced by bleeding to 90, 70, and 50 mmHg MAP and maintained for 15 min at each level, followed by retransfusion. HHR resulted in a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the MCA in vitro. Relaxations induced by the nitric oxide (NO) donor SIN-1 remained unaltered. In vitro treatment of the vessels with SOD (150 U/ml), facilitated the acetylcholine-induced relaxations both in the control arteries and in the vessels after HHR. In the vessel rings from cats that received in vivo SOD (10 mg/kg initial bolus, followed by 0.1-mg/kg/min infusion) during HHR, cholinergic relaxations were more pronounced than in the HHR untreated cats. The ATP-induced relaxations, however, remained attenuated after SOD treatment, except for the highest dose (10(-5) M) that was applied.


CONCLUSIONS
Superoxide release attenuates the endothelium-dependent relaxation by acetylcholine both in control arteries and after HHR in vitro. The protective effect of in vivo SOD treatment on cerebrovascular endothelium-dependent reactivity in cats suggests that superoxide free radicals contribute to the development of the endothelium dysfunction in MCA rings after HHR.
Szabó
C
C
Department of Neurology, Medical School University of Pennsylvania, Philadelphia, USA.
Csáki
C
C
Benyó
Z
Z
Marczis
J
J
Reivich
M
M
Kovách
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001804:Blood Transfusion, Autologous; D002415:Cats; D002536:Cerebral Arteries / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006470:Hemorrhage / Q000150:complications*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D013482:Superoxide Dismutase; D000109:Acetylcholine