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Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

Abstract
Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.
AuthorsKathryn R Walsh, Jill T Kuwabara, Joon W Shim, Richard D Wainford
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 310 Issue 2 Pg. R115-24 (Jan 15 2016) ISSN: 1522-1490 [Electronic] United States
PMID26608659 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2016 the American Physiological Society.
Chemical References
  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Slc12a3 protein, rat
  • Sodium Chloride Symporter Inhibitors
  • Sodium Chloride, Dietary
  • Solute Carrier Family 12, Member 3
  • Hydrochlorothiazide
  • Losartan
  • Norepinephrine
Topics
  • Angiotensin II Type 1 Receptor Blockers (pharmacology)
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Blood Pressure
  • Disease Models, Animal
  • Hydrochlorothiazide (pharmacology)
  • Hypertension (drug therapy, etiology, metabolism, physiopathology)
  • Kidney (drug effects, metabolism, physiopathology)
  • Losartan (pharmacology)
  • Male
  • Natriuresis
  • Norepinephrine
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System
  • Sodium Chloride Symporter Inhibitors (pharmacology)
  • Sodium Chloride, Dietary (blood)
  • Solute Carrier Family 12, Member 3 (drug effects, metabolism)
  • Sympathetic Nervous System (metabolism, physiopathology)
  • Time Factors

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