Protective effects of nicotinamide against nitric oxide-mediated delayed vascular failure in endotoxic shock: Potential involvement of polyADP ribosyl synthetase

Basilia Zingarelli, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Nitric oxide (NO) produced by the inducible isoform of nitric oxide synthase contributes to the hypotension and vascular hyporeactivity in shock. Nicotinamide is protective against the cytotoxic effects of exogenous and endogenous NO in vitro. We investigated the effect of nicotinamide on the cellular energetic and vascular failure in a rat model of endotoxin shock. Administration of nicotinamide to rats, starting at 1 h after bacterial lipopolysaccharide, maintained higher blood pressure levels, without affecting induction of nitric oxide synthase. Nicotinamide treatment prevented the lipopolysaccharide-induced decrease in mitochondrial respiration and intracellular NAD+ levels in peritoneal macrophages and improved the contractility of the thoracic aorta ex vivo. Thus, nicotinamide protects against the delayed, NO-mediated vascular failure in endotoxic shock. Its actions are unrelated to inhibition of NO biosynthesis but may be related to inhibition of the NO-mediated activation of an energy-consuming DNA repair cycle triggered by polyADP ribose synthetase.

Original languageEnglish (US)
Pages (from-to)258-264
Number of pages7
JournalShock
Volume5
Issue number4
StatePublished - Apr 1996
Externally publishedYes

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Niacinamide
Ligases
Septic Shock
Blood Vessels
Nitric Oxide
Lipopolysaccharides
Shock
Ribose
Peritoneal Macrophages
Nitric Oxide Synthase Type II
Thoracic Aorta
Endotoxins
Nitric Oxide Synthase
DNA Repair
NAD
Hypotension
Protein Isoforms
Respiration
Hypertension

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Protective effects of nicotinamide against nitric oxide-mediated delayed vascular failure in endotoxic shock : Potential involvement of polyADP ribosyl synthetase. / Zingarelli, Basilia; Salzman, Andrew L.; Szabo, Csaba.

In: Shock, Vol. 5, No. 4, 04.1996, p. 258-264.

Research output: Contribution to journalArticle

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