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NADPH oxidase inhibitors: new antihypertensive agents?

Abstract
NADPH oxidases have recently been shown to contribute to the pathogenesis of hypertension. The development of specific inhibitors of these enzymes has focused attention on their potential therapeutic use in hypertensive disease. Two of the most specific inhibitors, gp91ds-tat and apocynin, have been shown to decrease blood pressure in animal models of hypertension. Other inhibitors, including diphenylene iodonium, aminoethyl benzenesulfono fluoride, S17834, PR39, protein kinase C inhibitors, and VAS2870, have shown promise in vitro, but their in vivo specificity, pharmacokinetics, and effectiveness in hypertension remains to be determined. Of importance, the currently available antihypertensive agents angiotensin-converting enzyme inhibitors and angiotensin receptor blockers also effectively inhibit NADPH oxidase activation. Similarly, the cholesterol-lowering agents, statins, have been shown to attenuate NADPH oxidase activation. Although, antioxidants act to scavenge the reactive oxygen species produced by these enzymes, their effectiveness is limited. Targeting NADPH homologues may have a distinct advantage over current therapies because it would specifically prevent the pathophysiological formation of reactive oxygen species that contributes to hypertension.
AuthorsHolly C Williams, Kathy K Griendling
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 50 Issue 1 Pg. 9-16 (Jul 2007) ISSN: 0160-2446 [Print] United States
PMID17666910 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
Chemical References
  • Antihypertensive Agents
  • Antioxidants
  • Enzyme Inhibitors
  • Reactive Oxygen Species
  • NADPH Oxidases
Topics
  • Animals
  • Antihypertensive Agents (administration & dosage, pharmacology)
  • Antioxidants (administration & dosage, pharmacology)
  • Disease Models, Animal
  • Drug Delivery Systems
  • Enzyme Inhibitors (administration & dosage, pharmacology)
  • Humans
  • Hypertension (drug therapy, physiopathology)
  • NADPH Oxidases (antagonists & inhibitors)
  • Reactive Oxygen Species (metabolism)

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