Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats.
Oxygen radicals are known to be produced by the cerebral vasculature during acute, pressor-induced hypertension and are also known to inactivate endothelium-derived relaxing factor. The objective of our present study was to determine if the oxygen radical scavenger superoxide dismutase (24,000 units/kg plus 1,600 units/kg/min) alters the pressor, cerebral blood flow, and mortality responses to systemic norepinephrine in rats. Increasing doses (0.01-30 micrograms/kg i.v.) of norepinephrine were given by bolus injection to eight rats, and changes in the cortical microcirculatory blood flow were measured by laser-Doppler flowmetry. Superoxide dismutase shifted the norepinephrine-blood pressure and -cerebral blood flow dose-response curves moderately, but significantly, to the right such that it took more norepinephrine to reach a given blood pressure. However, superoxide dismutase had no effect on the autoregulation of cerebral blood flow. Additionally, whereas five (63%) of the eight control rats died after the 10 micrograms/kg norepinephrine dose, all eight rats treated with superoxide dismutase survived this dose. The mechanism by which superoxide dismutase reduced mortality is uncertain. The blood pressure and cerebral blood flow results suggest that superoxide dismutase prevents oxygen radicals from destroying endothelium-derived relaxing factors, which reduce the pressor effects of norepinephrine.
Zhang
X M
XM
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Ellis
E F
EF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*
D013482:Superoxide Dismutase; D009638:Norepinephrine