ROLE OF CENTRAL CATECHOLAMINERGIC PATHWAYS IN THE ACTIONS OF ENDOGENOUS ANG-II ON SYMPATHETIC REFLEXES

In the present study, we examined the effect of blockade of the brain stem renin-angiotensin system on renal sympathetic baroreflexes and ch emoreflexes in conscious rabbits and examined the role of central cate cholaminergic pathways in these responses. Eleven rabbits underwent pr eliminary surgical instrumentation and pretreatment with central B-hyd roxydopamine (6-OHDA, 500 mu g/kg) or ascorbic acid 6 wk before the co mmencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O-2 + 3% CO2) before and afte r central administration of either Ringer solution, the ANG II recepto r antagonist losartan (10 mu g), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased th e upper plateau and the range of the mean arterial pressure (MAP)-rena l sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) i n intact rabbits, whereas this effect was not observed in 6-OHDA-pretr eated rabbits. Hypoxia elicited an increase in resting RSNA (111% in i ntact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upp er plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and en alaprilat increased the RSNA upper plateau in intact rabbits but had n o effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rat e baroreflex curves were observed. Thus the effect of losartan to incr ease RSNA, particularly during hypoxia and baroreceptor unloading, bei ng abolished by central noradrenergic depletion suggests that the endo genous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergi c pathways.