Infection is a major complication of patients with diabetes, and endotoxemic
shock is a serious complication during
sepsis. The purpose of this study was to determine whether the action of bacterial
lipopolysaccharide (LPS) on vasocontractility is altered in diabetic vessels. Diabetes was induced in 10-week-old Wistar rats by an
intraperitoneal injection of
streptozotocin. LPS-induced increase in cGMP (cyclic
guanosine 3',5'-monophosphate) level was lower in aortae from
streptozotocin-induced hyperglycemic (diabetic) rats than in those from vehicle-injected control rats, while LPS-induced
nitric oxide production was not different in the diabetic and control aortae.
Phenylephrine-induced contraction of diabetic aortae was lower than that of the control aortae. LPS treatment resulted in depression of contractile response to
phenylephrine in both diabetic and control aortae, and the degree of depression was much lower in diabetic aortae. Treatment with N monomethyl
l-arginine (
l-NMMA) prevented diminution of
phenylephrine-induced contraction of the aortae after LPS stimulation, and the degree of the preventive effect by
l-NMMA was significantly lower in diabetic aortae than in the control aortae.
Protein expression of
inducible nitric oxide synthase detected by Western blot analysis was not different in the diabetic and control aortae. The decrease in cGMP production after LPS stimulation in diabetic aortae was not prevented by treatment of the aortae with
superoxide dismutase but was partially prevented by that with
Tiron (4,5-dihydroxy-1,3-benzene disulfonic acid), a cell-permeable scavenger of
reactive oxygen species. These results suggest that LPS-induced depression of vasocontractility is attenuated in diabetic aortae due to a decrease in
nitric oxide-stimulated cGMP production, probably resulting from increased inactivation of inducible
nitric oxide by excessive intracellular oxidative stress. It is concluded that contractility of aortae from
streptozotocin-induced hyperglycemic rats may be less affected by LPS during
endotoxemia.