Nicotinamide-inhibited vasoconstriction: lack of dependence on agonist signalling pathways

Eur J Pharmacol. 1999 Jun 18;374(2):213-20. doi: 10.1016/s0014-2999(99)00323-4.


Previously, we have shown that nicotinamide inhibits both high [K+]- and phenylephrine-induced constrictions in a dose-dependent manner in rat tail arteries. We have now investigated the effect of nicotinamide on intracellular signalling pathways in vascular smooth muscle. Nicotinamide (8.2 mM) reduced the response to phenylephrine- and [Arg8]vasopressin-induced constrictions by means of 72.9+/-6.9 and 51.8+/-5.7%, respectively. It also blocked phenylephrine-induced constrictions in the absence of a functional endothelium (P < 0.0136). In addition, pre-treatment of the artery with nifedipine (10 mM) also failed to inhibit nicotinamide's activity (P < 0.0178). Moreover, nicotinamide significantly reduced the sensitivity to phenylephrine in Ca2+-free Krebs' solution (P < 0.0152). Continuous perfusion of maximal concentrations of ryanodine or thapsigargin significantly inhibited the response to phenylephrine; the addition of nicotinamide (8.2 mM) caused a significant additional inhibition when compared to the effect of ryanodine (P < 0.0006) or thapsigargin (P<0.037) alone. In addition, beta-escin (0.02%) permeabilisation and Ca2+ (2.5 mM)-mediated constriction was also significantly attenuated by nicotinamide (P < 0.0001). However, phorbol ester-induced constriction was not attenuated by nicotinamide. This would suggest that nicotinamide directly inhibits vascular smooth muscle cell contraction and is unlikely to act via blockage of external Ca2+ entry or release of Ca2+ from intracellular stores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / pharmacology
  • Calcium Signaling / physiology
  • Drug Interactions
  • Endothelium / metabolism*
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Niacinamide / pharmacology*
  • Perfusion
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology


  • Vasoconstrictor Agents
  • Arginine Vasopressin
  • Phenylephrine
  • Niacinamide