APStracts 2:0336H, 1995.

Sympatho-excitatory and pressor responses to increased brain sodium and "ouabain" are mediated via brain angiotensin ii. Huang, Bing S., Frans H. H. Leenen. University of Ottawa Heart Institute, Hypertension Unit

APStracts 2:0336H, 1995.

Intra-cerebroventricular (icv) administration of hypertonic saline, ouabain, brain ouabain-like activity ("ouabain"), or angiotensin II (Ang II) causes sympatho-excitatory and pressor effects in rats. To clarify the possible interaction between increased brain sodium, brain "ouabain" and the brain renin angiotensin system (RAS), in conscious Wistar rats increases in BP, HR and renal sympathetic nerve activity (RSNA) in response to icv 0.3 M NaCl, ouabain and Ang II were recorded, before and after icv pretreatment with AT1 blocker losartan, antibody Fab fragments (DigibindR), or as control, [delta]-globulins. These Fab fragments bind ouabain and brain "ouabain" with high affinity. The vasopressin (AVP) antagonist D-(CH2)5Try-(Me)AVP (30 Ng/kg) was injected intravenously before each icv injection. Icv 0.3 M NaCl (3.8 Nl/min for 10 min), ouabain (0.3 and 0.6 Ng) and Ang II (10 and 30 ng) caused similar pressor responses. However, the extent of HR and RSNA responses to Ang II was smaller than those to 0.3 M NaCl and ouabain. Icv losartan (10 and 20 Ng) blocked responses to Ang II and 0.3 M NaCl and significantly (pressor response by 50-70%; RSNA and HR by 60-80%) attenuated the responses to ouabain. In contrast, icv Fab fragments (66 Ng) blocked only the responses to 0.3 M NaCl and ouabain, and did not affect the responses to Ang II. These results suggest that an acute rise in brain sodium concentration increases brain "ouabain", and the latter exerts its sympatho -excitatory and pressor effects at least partly via activation of the brain RAS.

Received 25 May 1995; accepted in final form 25 July 1995.
APS Manuscript Number H487-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.