Effect of linsidomine on the human radial artery

Clin Sci (Lond). 2002 Jul;103(1):1-6. doi: 10.1042/cs1030001.

Abstract

The response of the human radial artery to a direct NO donor, linsidomine or 3-morpholino-sydnonimine (Sin 1), in the therapeutic management of peri-operative spasm may increase the patency rates of these grafts in the short, medium and long term. Evaluation of the effects of Sin 1 on the human radial artery is of even greater interest as it has not been published previously. Ninety-six human radial artery rings were studied with two protocols. Rings were mounted in an isolated organ bath between two stainless steel metallic rods connected to stress gauges. Protocol 1 studied the vasorelaxant effect of Sin 1 and nitroglycerin (TNT). Protocol 2 studied the reactivity of the radial artery to the vasoconstrictor agents arginine vasopressin (AVP) and angiotensin II (ANG II). The vasorelaxant effect of Sin 1 on the human radial artery was comparable with that of TNT, but with no tolerance effect. After Sin 1 pre-incubation, the vasoconstrictor effect of ANG II was abolished, whereas AVP induced maximum vasoconstriction similar to that of the control (not statistically significant), but with a shift in the EC50 to higher concentrations, EC50=15+/-20 nM. Sin 1 vasorelaxation of rings precontracted by ANG II was maximal, whereas after contraction by AVP, relaxation remained less than 70%; Sin 1 is a potent vasorelaxant on the human radial artery, which does not exhibit cross-tolerance with nitrates. This compound may be used pre- or post-operatively, and would undoubtedly be of benefit in the peri-operative preparation bath.

MeSH terms

  • Angiotensin II / pharmacology
  • Arginine Vasopressin / pharmacology
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Culture Techniques
  • Dose-Response Relationship, Drug
  • Humans
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology*
  • Nitroglycerin / pharmacology
  • Radial Artery / drug effects*
  • Radial Artery / physiology
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology*

Substances

  • Cholinergic Agonists
  • Vasodilator Agents
  • Angiotensin II
  • Arginine Vasopressin
  • linsidomine
  • Carbachol
  • Molsidomine
  • Nitroglycerin