Reduced NAD(P)H oxidase in low renin hypertension: Link among angiotensin II, atherogenesis, and blood pressure

Ming Sheng Zhou, Ivonne H Schulman, Patrick J. Pagano, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Endothelial dysfunction (ED) complicates hypertension and is a precursor of atherosclerosis. Reduced NO bioactivity, because of increased reduced NAD(P)H oxidase-derived reactive oxygen species (ROS), plays a critical role in ED. gp91phox, predominantly expressed in the endothelium and adventitia, is a subunit of NAD(P)H oxidase important for its activation in response to angiotensin (Ang) II. Human atherosclerotic plaques are heavy laden with gp91phox. We have shown that in Dahl salt-sensitive (DS) rats, a paradigm of low renin salt-sensitive (SS) hypertension in humans, Ang II receptor blockade normalizes ROS production and endothelium-dependent relaxation (EDR) without significantly affecting systolic blood pressure (SBP). To additionally elucidate the mechanisms involved in the functional association of Ang II in SS hypertension, we administered a cell-permeable inhibitor of the assembly of p47phox with gp91phox in NAD(P)H oxidase, gp91ds-tat (10 mg/kg body weight, 3 weeks by minipump), to DS rats fed a 4% salt diet. Control rats received either vehicle or an inactive scramb-tat peptide. Vehicle-treated DS developed hypertension (SBP 168±5 mm Hg), left ventricular hypertrophy (LVH), proteinuria, impaired EDR, and increased aortic ROS production (superoxide 115% and peroxynitrite 157%) and expression of the proatherogenic molecules LOX-1 (130%) and MCP-1 (166%). gp91ds-tat, but not scramb-tat, normalized ROS and EDR, as well as LOX-1 and MCP-1, despite nonsignificant effects on SBP (159±5 mm Hg; P>0.05), left ventricular hypertrophy, and proteinuria. Our findings support the notion that in SS hypertension, activation of NAD(P)H oxidase promotes ED and atherogenesis via decreased nitric oxide bioactivity and increased LOX-1 and MCP-1, independent of blood pressure.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalHypertension
Volume47
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

NADPH Oxidase
Renin
Angiotensin II
Atherosclerosis
Blood Pressure
Hypertension
Salts
Endothelium
Reactive Oxygen Species
Inbred Dahl Rats
Left Ventricular Hypertrophy
Proteinuria
Adventitia
Angiotensin Receptors
Peroxynitrous Acid
Atherosclerotic Plaques
Superoxides
Nitric Oxide
Body Weight
Diet

Keywords

  • Atherosclerosis
  • Endothelium
  • Free radicals
  • Hypertension
  • Sodium

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Reduced NAD(P)H oxidase in low renin hypertension : Link among angiotensin II, atherogenesis, and blood pressure. / Zhou, Ming Sheng; Schulman, Ivonne H; Pagano, Patrick J.; Jaimes, Edgar A.; Raij, Leopoldo.

In: Hypertension, Vol. 47, No. 1, 01.01.2006, p. 81-86.

Research output: Contribution to journalArticle

Zhou, Ming Sheng ; Schulman, Ivonne H ; Pagano, Patrick J. ; Jaimes, Edgar A. ; Raij, Leopoldo. / Reduced NAD(P)H oxidase in low renin hypertension : Link among angiotensin II, atherogenesis, and blood pressure. In: Hypertension. 2006 ; Vol. 47, No. 1. pp. 81-86.
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