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Nitric oxide and superoxide interactions in the kidney and their implication in the development of salt-sensitive hypertension.

Abstract
1. Enhanced superoxide (O2(-)) activity as a result of the inhibition of the superoxide dismutase (SOD) enzyme results in vasoconstrictor and antinatriuretic responses in the canine kidney; these responses were shown to be greatly enhanced during inhibition of nitric oxide synthase (NOS). Glomerular filtration rate remained mostly unchanged during SOD inhibition in the intact nitric oxide (NO) condition, but was markedly reduced during NOS inhibition. These findings indicate that endogenous NO has a major renoprotective effect against O2(-) by acting as an anti-oxidant. Nitric oxide synthase inhibition was also shown to enhance endogenous O2(-) activity. 2. Experiments in our laboratory using dogs, rats and gene knockout mice have shown that renal vasoconstrictor and antinatriuretic responses to acute or chronic angiotensin (Ang) II administration are mediated, in part, by O2(-) generation. In the absence of NO, enhanced O2(-) activity largely contributes to AngII-induced renal tubular sodium reabsorption. Acute or chronic treatment with the O2(-) scavenger tempol in experimental models of hypertension (induced by chronic low-dose treatment with AngII and NO inhibitors) causes an improvement in renal haemodynamics and in excretory function, abolishes salt sensitivity and reduces blood pressure. 3. The present mini review also discusses related studies from many other laboratories implicating a role for O2(-) and its interaction with NO in the development of salt-sensitive hypertension. 4. Overall, the collective data support the hypothesis that an imbalance between the production of NO and O2(-) in the kidney primarily determines the condition of oxidative stress that alters renal haemodynamics and excretory function leading to sodium retention and, thus, contributes to the development of salt-sensitive hypertension.
AuthorsDewan S A Majid, Libor Kopkan
JournalClinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 34 Issue 9 Pg. 946-52 (Sep 2007) ISSN: 0305-1870 [Print] Australia
PMID17645645 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antioxidants
  • Enzyme Inhibitors
  • Superoxides
  • Angiotensin II
  • Nitric Oxide
  • Sodium Chloride
  • Nitric Oxide Synthase
Topics
  • Angiotensin II (metabolism)
  • Animals
  • Antioxidants (pharmacology)
  • Blood Pressure (drug effects)
  • Disease Models, Animal
  • Dogs
  • Enzyme Inhibitors (pharmacology)
  • Hypertension (metabolism, physiopathology)
  • Kidney (metabolism, physiopathology)
  • Mice
  • Natriuresis (drug effects)
  • Nitric Oxide (metabolism)
  • Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
  • Oxidative Stress (drug effects)
  • Rats
  • Sodium Chloride (metabolism)
  • Superoxides (metabolism)

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