Cofactors of constitutive nitric oxide synthase and endothelium-dependent relaxations in canine femoral veins

D. A. Lewis, K. S. Rud, Virginia M Miller

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Enzymatic production of nitric oxide (NO) in arterial endothelial cells requires the cofactors calmodulin and nicotinamide adenine dinucleotide phosphate (NADPH). Experiments were designed in investigate whether these cofactors are required for endothelium-dependent relaxations in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. All rings were incubated with indomethacin (1 x 10-5 M). In separate sets of experiments, rings were incubated with calmidazolium (1 x 10-5 M), fendiline (1 x 10- 6 M), both inhibitors of calmodulin or diphenylene-iodonium (1 x 10-5 M; DPI) an inhibitor of NADPH. Concentration-response curves were obtained for acetylcholine (ACh), ADP, thrombin, A23187, and NO in rings contracted with a submaximal concentration of prostaglandin F(2α) (PGF(2α)) in the presence of the inhibitors and compared with a solvent control (dimethyl sulfoxide, DMSO). Relaxations to ACh, ADP, and thrombin were reduced by the inhibitors of both cofactors. Relaxations to A23187 were reduced by inhibitors of calmodulin but not NADPH; inhibitors of both NADPH and calmodulin caused no significant reduction in relaxations to NO. These data suggest that endothelium-dependent relaxations in canine femoral veins are mediated by factor(s) that are partly dependent on calmodulin or NADPH as cofactors for their production or release.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume22
Issue number3
StatePublished - 1993

Keywords

  • Calmodulin
  • Endothelium-derived relaxing factors
  • NADPH
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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