Nicotinamide increases systemic vascular resistance in ovine endotoxemia

Abstract

The PARP inhibitor nicotinamide attenuates impairment of cardiovascular function during endotoxemia. In addition, PARP activation may be involved in endotoxin-induced liver injury.

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia

“…The release of NO degradation products was lower in endotoxin‐induced pneumonia in PARP‐deficient mice [29]. Recently, two published studies show effect of nicotinamide in animal endotoxin models [30,31]. Treatment with nicotinamide stabilized haemodynamics in porcine hyperdynamic endotoxaemia, using a dose of intravenous nicotinamide 10 mg/kg/h for 12 h [30].…”

“…In the same study nicotinamide failed to counteract the endotoxin‐induced deterioration of the hepato‐splanchnic energy metabolism, an effect, potentially ascribed to inadequate dosing of nicotinamide [30]. Also, protective effects of nicotinamide on haemodynamics as well as a hepatotoxic‐preventing effect were found in an ovine model of hyperdynamic endotoxaemia, using a bolus of 40 mg/kg followed by 10 mg/kg/h nicotinamide for 24 h [31].…”

Nicotinamide: a jack of all trades (but master of none?)

“…In the recent issue of Intensive Care Medicine, Scharte and colleagues [4] and Stehr and colleagues [5] report their investigations on various aspects of nicotinamide (as a PARP inhibitor) in large animal models of shock. Physiologically, nicotinamide is a byproduct of the enzymatic reaction of NAD + and PARP, and therefore serves as an endogenous feedback inhibitor of the enzyme.…”

“…These effects include improvement in survival, reported as early as 1974 [7]. The two current papers [4,5] add important new information on the beneficial effects of nicotinamide in large animal models of circulatory shock. In 1996, we reported higher blood pressure levels in endotoxemic rats with nicotinamide treatment, as well as a prevention of the endotoxin-induced decrease in mitochondrial respiration and intracellular NAD + levels in peritoneal macrophages and improvements in the contractility of the thoracic aorta ex vivo [9].…”