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 chemoreflexes in conscious rabbits and examined the role of central catecholaminergic pathways in these responses. Eleven rabbits underwent preliminary surgical instrumentation and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 micrograms/kg) or ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after central administration of either Ringer solution, the ANG II receptor antagonist losartan (10 micrograms), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and enalaprilat increased the RSNA upper plateau in intact rabbits but had no effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex curves were observed. Thus the effect of losartan to increase RSNA, particularly during hypoxia and baroreceptor unloading, being abolished by central noradrenergic depletion suggests that the endogenous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergic pathways.
Baker Medical Research Institute, Victoria, Australia.
E A
EA
Gaudet
S J
SJ
Godwin
G A
GA
Head
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D011817:Rabbits; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D016627:Oxidopamine; D015773:Enalaprilat; D019808:Losartan; D001205:Ascorbic Acid