In Salt-Sensitive Hypertension, Increased Superoxide Production Is Linked to Functional Upregulation of Angiotensin II

Ming Sheng Zhou, Ahmed G. Adam, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4% NACl) diet. Control rats received a normal-salt (0.5% NaCl, [NS]) diet. Prehypertensive DS rats (systolic blood pressure [SBP] 138±2 mm Hg) manifested a 35% increase (P<0.05) in aortic superoxide (O2 -) production without evidence of end-organ damage. Hypertensive DS rats (SBP 214±11 mm Hg) had impaired endothelium-dependent relaxation (EDR) and increased aortic O2- production (320%), urinary isoprostane excretion (83%), aortic (20%) and left ventricular (LVH, 21%) hypertrophy, and proteinuria (124%). In prehypertensive DS rats, candesartan (10 mg · kg-1 · d-1) an Ang II type 1 receptor blocker (ARB), normalized O2- production. In hypertensive DS rats, the ARB decreased aortic O2- production by 71% and normalized EDR without affecting SBP (212±8 mm Hg), aortic hypertrophy, LVH, or proteinuria. Switching hypertensive DS rats to an NS diet did not affect SBP (208±8 mm Hg), LVH, aortic hypertrophy, or proteinuria and had minimal effects on O2- and EDR. Concomitant ARB administration plus a switch to an NS diet normalized SBP (138±8 mm Hg) as well as end-organ damage, Dahl salt-resistant rats fed an HS diet for 12 weeks did not show hypertension or increased O 2- production. Thus, SS hypertension might represent a specific vascular diathesis linked to functional upregulation of Ang II action (increased O2- synthesis) accompanied by insufficient NO bioavailability, which promotes severe endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)945-951
Number of pages7
JournalHypertension
Volume42
Issue number5
DOIs
StatePublished - Nov 1 2003

Keywords

  • Angiotensin II
  • Endothelium
  • Hypertension, sodium-dependent
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Internal Medicine

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