Chronic central infusion of angiotensin II potentiates cardiac sympathetic afferent reflex

The previous study in this laboratory has shown that the central gain of cardiac sympathetic afferent reflex (CSAR) is enhanced in heart failure dog and angiotensin II (Ang II) plays a role in this enhancement (Circulation, 94(8):1-132, 1996). The aim of this study is to determine if chronic central infusion of Ang II potentiates central gain of CSAR in normal dogs. A cerebroventricular cannula was inserted and an Ang II osmotic minipump was implanted subcutaneously. After chronic central infusion of Ang II (4 μg/h for 3 days), mean arterial pressure was significantly elevated (127.2 ± 2.1 vs. 111.8 ± 1.4 mm Hg, p<0.05) and water intake was significantly increased (51.9 ± 13.9 vs. 32.2 ± 4.8 ml/kg/day, p<0.05). CSAR was determined in α-chloralose (100 mg/kg, iv) anesthetized, sino-aortic denervated and vagotomized states. Renal sympathetic nerve activity (RSNA) response to electrical stimulation of the central ends of the left cardiac sympathetic nerves were compared between Ang II infused and sham dogs. RSNA response to a 30 seconds train of 10 V, 30 Hz, 1 ms pulses was significantly enhanced in the Ang II infused group compared to the sham group (17.4 ± 1.4 vs 10.6 ± 1.6 % of control, p<0.05). This enhanced CSAR in the Ang II infused group was prevented by ATI receptor antagonist, losartan (125 μg/kg, icv) (8.0 ± 3.1 vs. 17.4 ± 1.4 % of control, p<0.01). This result indicates that chronic central infusion of Ang II potentiates cardiac sympathetic afferent reflex and suggests that central elevated Ang II may play an important role in enhanced CSAR in heart failure state.