Sympathoexcitatory and pressor responses to increased brain sodium and ouabain are mediated via brain ANG II

Intracerebroventricular administration of hypertonic saline, ouabain, brain ouabainlike activity (OLA), or angiotensin II (ANG: II) causes sympathoexcitatory and presser effects in rats. To clarify the possible interaction between increased brain sodium, brain OLA, and the brain renin-angiotensin system (RAS), increases in mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in response to intracerebroventricular 0.3 M NaCl, ouabain, and ANG II were recorded in conscious Wistar rats before and after intracerebroventricular pretreatment with the angiotensin-receptor (AT(1)) blocker losartan, antibody Fab fragments (Digibind), or, as control, gamma-globulins. These Fab fragments bind ouabain and brain OLA with high affinity. The arginine vasopressin (AVP) antagonist [d(CH2)(5)Tyr(Me)]AVP (30 mu g/kg) was injected intravenously before each intracerebroventricular injection. Intracerebroventricularly administered 0.3 M NaCl (3.8 mu l/min for 10 min), ouabain (0.3 and 0.6 mu g), and ANG II (10 and 30 ng) caused similar presser responses. However, the extent of HR and RSNA responses to ANG II was smaller than those to 0.3 M NaCl and ouabain. Intracerebroventricular losartan (10 and 20 mu g) blocked responses to ANG II and 0.3 M NaCl and significantly attenuated the responses to ouabain (presser response by 50-70%; RSNA and HR by 60-80%). In contrast, intracerebroventricular Fab fragments (66 mu g) 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 OLA and the latter exerts its sympathoexcitatory and presser effects at least partly via activation of the brain RAS.