Effect of linsidomine on the human radial artery.
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.
Remadi
J P
JP
Cardiac Surgery Unit, Hopital Sud-Laênnec, 80054 Amiens, France. Remadi.Jean-Paul@chu-amiens.fr
Colas
B
B
Masson
H
H
Slama
M
M
Andréjack
M
M
D000804:Angiotensin II / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D017534:Radial Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D018679:Cholinergic Agonists; D014665:Vasodilator Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; C002385:linsidomine; D002217:Carbachol; D008981:Molsidomine; D005996:Nitroglycerin