We have previously shown that acute i.v. injection of the angiotensin-converting enzyme (ACE) inhibitor enalapril in diabetic rats evokes a baroreflex independent sympathoexcitatory effect that does not occur with angiotensin receptor blockade alone. As ACE inhibition also blocks bradykinin degradation, we sought to determine if bradykinin mediated this effect. Experiments were performed in conscious male Sprague Dawley rats, chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA), two weeks after streptozotocin (55 mg/kg i.v., diabetic, n=11) or citrate vehicle (normal, n=10). Enalapril (2.5 mg/kg iv) decreased MAP in normal rats (-15±3 mmHg), while a smaller response (-4±1 mmHg) occurred in diabetic rats. Despite these different depressor responses to enalapril, HR (+44±8 vs. +26±7 bpm) and RSNA (+90±21 vs +71±8 %baseline) increased similarly between the groups (P0.22 for both). Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 (10 µg/kg bolus followed by 0.8 µg/kg/min infusion) attenuated the decrease in MAP observed with enalapril in normal rats but had no effect in diabetic rats. Moreover, the normal group had smaller HR and RSNA responses (HR: +13±8 bpm; RSNA: +32±13 % baseline) that were abolished in the diabetic group (HR: -4±5 bpm; RSNA: -5±9 %baseline; P<0.05 vs pre-enalapril values). Additionally, bradykinin (20 µg/kg i.v.) evoked a larger, more prolonged sympathoexcitatory effect in diabetic compared to normal rats that was further potentiated after treatment with enalapril. We conclude that enhanced bradykinin signaling mediates the baroreflex independent sympathoexcitatory effect of enalapril in diabetic rats.