title: Brain angiotensinergic pathways mediate renal nerve inhibition by central hypertonic NaCl in conscious sheep.
abstract: The renal sympathetic responses to infusion of hypertonic solutions into the lateral cerebral ventricles were investigated in conscious sheep. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) containing 0.6 M NaCl, at 1 ml/h for 20 min, reduced renal sympathetic nerve activity (RSNA) by 81 +/- 5% (n = 6, P < 0.001). Plasma renin concentration also fell (P < 0.05), whereas arterial pressure increased by 6.4 +/- 0.7 mmHg (P < 0.01). Intracerebroventricular hypertonic sorbitol (0.9 M in CSF at 1 ml/h) had no effect. The AT1 receptor antagonist losartan (1 mg/h) abolished the plasma renin and arterial pressure responses to intracerebroventricular hypertonic saline and significantly reduced the fall in RSNA to 17 +/- 10% (P < 0.001). During intracerebroventricular hypertonic saline, the baroreflex relation of RSNA to diastolic pressure was shifted to the left and that to central venous pressure was abolished compared with control relations obtained by manipulating pressure with intravenous phenylephrine. These findings indicate that 1) RSNA is inhibited by a central mechanism that senses high sodium (or perhaps chloride) concentration rather than hypertonicity; 2) this inhibition occurs independently of reflexes from high- and low-pressure baroreceptors, although these may enhance the inhibition; and 3) inhibition of RSNA by hypertonic saline involves a central angiotensinergic pathway.
authors.affiliation: Howard Florey Institute of Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia. Clive_May.hfi@muwaye.unimelb.edu.au
authors.forename: C N
authors.initials: CN
authors.lastname: May
authors.forename: R M
authors.initials: RM
authors.lastname: McAllen
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation*; D019808:Losartan; D009433:Neural Inhibition; D009434:Neural Pathways / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000494:pharmacology; D012756:Sheep; D012964:Sodium / Q000134:cerebrospinal fluid; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; D012964:Sodium; D019808:Losartan