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 pressor 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 (AT1) 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)5Tyr(Me)]AVP (30 micrograms/ kg) was injected intravenously before each intracerebroventricular injection. Intracerebroventricularly administered 0.3 M NaCl (3.8 mul/min for 10 min), ouabain (0.3 and 0.6 microgram), 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. Intracerebroventricular losartan (10 and 20 micrograms) blocked responses to ANG II and 0.3 M NaCl and significantly attenuated the responses to ouabain (pressor response by 50-70%; RSNA and HR by 60-80%). In contrast, intracerebroventricular Fab fragments (66 micrograms) 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 pressor effects at least partly via activation of the brain RAS.
Huang
B S
BS
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Leenen
F H
FH
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D019808:Losartan; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007140:Immunoglobulin Fab Fragments; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; D010042:Ouabain; D012964:Sodium; D019808:Losartan