Oxidative stress impairs cardiac chemoreflexes in diabetic rats

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sha m- and STZ-treated rats were chronically treated with an antioxidant, vitam in E (60 mg/kg per os daily, started 2 days before STZ). Animals were studi ed 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympath etic afferent activities in response to stimulation of chemosensitive senso ry nerves in the heart by epicardial application of capsaicin (Caps) and br adykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 mug) evoked a vagal afferent mediated reflex depression of RSNA and MABP, w hich was significantly blunted in STZ-treated rats (P < 0.05). In vagal-den ervated rats, Caps and BK (1-10.0 <mu>g) evoked a sympathetic afferent-medi ated reflex elevation of RSNA and MABP, which also was significantly blunte d in STZ-treated rats (P, 0.05). Chronic vitamin E treatment effectively pr evented these cardiac chemoreflex defects in STZ-treated rats without alter ing resting blood glucose or hemodynamics. STZ-treated rats with insulin re placement did not exhibit impaired cardiac chemoreflexes. In afferent studi es, Caps and BK (0.1 g-10.0 mug) increased cardiac vagal and sympathetic af ferent nerve activity in a dose-dependent manner in sham- treated rats. The se responses were significantly blunted in STZ-treated rats. Vitamin E prev ented the impairment of afferent discharge to chemical stimulation in STZ r ats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac ch emosensitive nerve endings, and these disturbances can be prevented by chro nic treatment with vitamin E. These results suggest that oxidative stress p lays an important role in the neuropathy of this autonomic reflex in diabet es.