Proceedings of the High Blood Pressure Research Council of Australia - Blockade of central angiotensin II does not affect the reduction in renal sympathetic nerve activity following a volume load in heart failure rabbits

1. We investigated the role in sympathetic nerve regulation of endogenous a ngiotensin (Ang)II in the brain in heart failure by examining the effect of losartan on the resting mean arterial blood pressure (MAP), heart rate (HR ) and renal sympathetic nerve activity (RSNA) and the reflex reduction in R SNA elicited by acute volume expansion in conscious rabbits. 2. Heart failure was induced with doxorubicin (1 mg/kg, i.v., twice weekly for 6 weeks). On the experimental day, MAP, HR and RSNA were recorded in co nscious rabbits before and after losartan (10 mu g; n = 6) or Ringer's (con trol; n = 5) injected in the fourth brain ventricle. Animals were then admi nistered an acute volume load with the plasma expander Haemaccel (Hoechst M arion Roussel, Lane Cove, NSW, Australia; 2 mL/min, i.v., for 30 min). 3. Losartan did not significantly affect the resting basal levels of MAP, H R and RSNA. There was no significant difference between losartan- and Ringe r's-treated animals. 4. Volume expansion in the control group elicited a significant reduction o f 40% in RSNA. In the losartan-treated group, a similar reduction (42%) was observed. There was no significant difference between the treatments. The administration of losartan did not significantly affect MAP and HR during v olume expansion compared with the control group. 5. We conclude that AngII in the brainstem does not play a major role in th e maintenance of resting MAP, HR and RSNA or in the reflex reduction in RSN A elicited by volume expansion in the conscious rabbit with doxorubicin-ind uced heart failure.