POSSIBLE SUPEROXIDE RADICAL-INDUCED ALTERATION OF VASCULAR REACTIVITYIN AORTAS FROM STREPTOZOTOCIN-TREATED RATS

We investigated the possible involvement of the Superoxide (.O2-) radi cal in alterations of vascular reactivity and phosphoinositide (PI) tu rnover in aortas from streptozotocin (STZ)-induced diabetic (4 week) r ats. STZ treatment increased the maximal contractile response of the a orta to norepinephrine (NE), phenylephrine (PE) and high K+, whereas t he sensitivity remained unaltered. Ca++-induced contractions in the pr esence of maximally effective concentrations of PE and K+ were also au gmented after STZ treatment. The increased maximal response was associ ated with both decreased endothelium-dependent relaxation and increase d NE-induced PI turnover. Pyrogallol (PYR), a potent .O2- generating a gent, did not affect basal tone or PI turnover but, depending on conce ntrations, it significantly increased or decreased both the contractil e response to PE and NE-induced PI turnover in control aorta. In contr ast, PYR decreased NE-induced PI turnover in diabetic aorta. The malon dialdehyde content of liver, serum and aorta, and of .O2- from aorta o f diabetic rats, were increased significantly. Copper catalyzed oxidat ion of ascorbic acid resulted in contraction followed by relaxation, d epending upon the ascorbic acid concentration in both control and diab etic aorta. Pretreatment with superoxide dismutase (300 U/ml) prevente d the PYR-induced potentiation of the PE contraction, but not of NE PYR-induced PI turnover in control aorta and decreased further NE + PY R-induced PI turnover in diabetic aorta. The present findings indicate that .O2- may be responsible, at least in part, for the impaired endo thelial integrity, enhanced alpha adrenergic receptor-mediated PI turn over and augmented contractility, possibly through modification of cal cium channels in STZ-induced short-term (4 week) diabetic rat aorta.