Central activation of cardiac vagal nerve by α

To elucidate the abnormality of cardiac vagal control in streptozotocin-induced type 1 diabetic rats, we measured left ventricular myocardial interstitial acetylcholine (ACh) release in response to α2-adrenergic stimulation as an index of in vivo cardiac vagal nerve activity. A cardiac microdialysis technique was applied to the rat left ventricle, and the effect of α2-adrenergic stimulation by intravenous medetomidine (100 μg/kg) on myocardial interstitial ACh levels was examined in anesthetized diabetic rats (4-6 weeks after intraperitoneal streptozotocin) and age-matched control rats (protocol 1). The effect of electrical vagal nerve stimulation on ACh levels was also examined in separate rats (protocol 2). In protocol 1, medetomidine increased the ACh levels in control (from 1.76 ± 0.65 to 3.13 ± 1.41 nM, P < 0.05, n = 7) but not in diabetic rats (from 2.01 ± 0.47 to 1.62 ± 0.34 nM, not significant, n = 7). In protocol 2, electrical vagal nerve stimulation at 20 Hz significantly increased the ACh levels in both control (from 1.49 ± 0.26 to 6.39 ± 1.81 nM, P < 0.001, n = 6) and diabetic rats (from 1.77 ± 0.54 to 6.98 ± 1.38 nM, P < 0.001, n = 6). In conclusion, medetomidine-induced central vagal activation was impaired in diabetic rats, whereas peripheral cardiac vagal control of ACh release was preserved. The impairment of central vagal activation may lead to relative sympathetic predominance and promote cardiovascular complications in diabetes.