Possible superoxide radical-induced alteration of vascular reactivity in aortas from streptozotocin-treated rats

Abstract

We investigated the possible involvement of the superoxide (.O2-) radical in alterations of vascular reactivity and phosphoinositide (PI) turnover in aortas from streptozotocin (STZ)-induced diabetic (4 week) rats. STZ treatment increased the maximal contractile response of the aorta to norepinephrine (NE), phenylephrine (PE) and high K+, whereas the sensitivity remained unaltered. Ca(++)-induced contractions in the presence of maximally effective concentrations of PE and K+ were also augmented after STZ treatment. The increased maximal response was associated with both decreased endothelium-dependent relaxation and increased NE-induced PI turnover. Pyrogallol (PYR), a potent .O2- generating agent, did not affect basal tone or PI turnover but, depending on concentrations, it significantly increased or decreased both the contractile response to PE and NE-induced PI turnover in control aorta. In contrast, PYR decreased NE-induced PI turnover in diabetic aorta. The malondialdehyde content of liver, serum and aorta, and of .O2- from aorta of diabetic rats, were increased significantly. Copper catalyzed oxidation of ascorbic acid resulted in contraction followed by relaxation, depending upon the ascorbic acid concentration in both control and diabetic aorta. Pretreatment with superoxide dismutase (300 U/ml) prevented the PYR-induced potentiation of the PE contraction, but not of NE+PYR-induced PI turnover in control aorta and decreased further NE+PYR-induced PI turnover in diabetic aorta. The present findings indicate that .O2- may be responsible, at least in part, for the impaired endothelial integrity, enhanced alpha adrenergic receptor-mediated PI turnover and augmented contractility, possibly through modification of calcium channels in STZ-induced short-term (4 week) diabetic rat aorta.