Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: influence of dietary sodium.
OBJECTIVE
Administration of angiotensin II (angII) into the cerebral ventricles or specific brain sites impairs arterial baroreflex regulation of renal sympathetic nerve activity (SNA). Further insight into this effect was derived from: (a) using specific non-peptide angII receptor antagonists to assess the role of endogenous angII acting on angII receptor subtypes, (b) microinjection of angII receptor antagonists into brain sites behind an intact blood-brain barrier to assess the role of endogenous angII of brain origin and (c) alterations in dietary sodium intake, a known physiological regulator of activity of the renin-angiotensin system (RAS), to assess the ability to physiologically regulate the activity of the brain RAS.


METHODS
In rats in balance on low, normal or dietary sodium intake, losartan or candesartan was injected into the lateral cerebral ventricle or the rostral ventrolateral medulla (RVLM) and the effects on basal renal SNA and the arterial baroreflex sigmoidal relationship between renal SNA and arterial pressure were determined.


RESULTS
With both routes of administration, the effects were proportional to the activity of the RAS as indexed by plasma renin activity (PRA). The magnitude of both the decrease in basal renal SNA and the parallel resetting of arterial baroreflex regulation of renal SNA to a lower arterial pressure was greatest in low-sodium rats with highest PRA and least in high-sodium rats with lowest PRA. Disinhibition of the paraventricular nucleus (PVN) by injection of bicuculline causes pressor, tachycardic and renal sympathoexcitatory responses mediated via an angiotensinergic projection from PVN to RVLM. In comparison with responses in normal sodium rats, these responses were greatly diminished in high-sodium rats and greatly enhanced in low-sodium rats.


CONCLUSIONS
Physiological changes in the activity of the RAS produced by alterations in dietary sodium intake regulate the contribution of endogenous angII of brain origin in the modulation of arterial baroreflex regulation of renal SNA.
DiBona
G F
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Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, IA 52242, USA.
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology; D002552:Cerebral Ventricles / Q000502:physiology; D007668:Kidney / Q000294:innervation*; D019808:Losartan / Q000494:pharmacology; D008526:Medulla Oblongata / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D051381:Rats; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012982:Sodium, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D012083:Renin; D019808:Losartan; C081643:candesartan; D001640:Bicuculline