AT1-receptor blockade in the hypothalamic PVN reduces central hyperosmolality-induced renal sympathoexcitation

H. U.I. Qing Chen, Glenn M. Toney

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are innervated by osmotic-sensitive regions of the lamina terminalis, receive input from ANG II-containing cells, and express AT1 ANG II receptors. Therefore, we hypothesized that ANG II actions within the PVN could underlie hyperosmolality-induced increases in renal sympathetic nerve activity (RSNA). In anesthetized barore-ceptor-denervated rats, graded concentrations of NaCl (0.30, 0.9, 1.5, and 2.1 osmol/l) were injected (300 μl) centrally via the internal carotid artery (ICA) and produced corresponding increases in mean arterial pressure (MAP) and RSNA. In addition, equivalent hyperosmotic loads (1.5 osmol/l) of NaCl, glucose, and mannitol each significantly (P < 0.05) increased MAP and RSNA. The same stimuli had no effect when administered intravenously. Bilateral PVN microinjections (100 nl) of the AT1-receptor antagonist losartan (80 nmol) before osmotic challenge had no effect on resting RSNA but significantly (P < 0.05) reduced RSNA responses to hyperosmotic NaCl (n = 7), glucose (n = 6), and mannitol (n = 6). Increases in RSNA evoked by hyperosmotic NaCl were significantly (P < 0.05) attenuated ∼20 min after losartan injection and recovered within 60-120 min. In contrast, losartan outside the PVN as well as vehicle (saline) within the PVN failed to alter RSNA responses to ICA hyperosmotic NaCl. Results suggest that elevated RSNA after central sodium/osmotic activation is mediated, at least in part, by a synaptic mechanism involving AT1-receptor activation within the PVN.

Original languageEnglish (US)
Pages (from-to)R1844-R1853
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number6 50-6
StatePublished - Dec 1 2001

Keywords

  • Angiotensin II
  • Osmolality
  • Paraventricular nucleus
  • Sodium
  • Sympathetic nerve activity; arterial pressure

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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