The group at C2 of N-ethylnicotinamide determines the vasodilator potencies and mechanisms of action of nicorandil and its congeners in canine coronary arteries

  title={The group at C2 of N-ethylnicotinamide determines the vasodilator potencies and mechanisms of action of nicorandil and its congeners in canine coronary arteries},
  author={Keisuke Satoh and Hiroaki Yamada and Fumiya Yoneyama and Norio Taira},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  • K. Satoh, H. Yamada, N. Taira
  • Published 1 November 1991
  • Chemistry, Medicine
  • Naunyn-Schmiedeberg's Archives of Pharmacology
SummaryThe relaxant mechanisms of action of nicorandil and its congeners (SG-86, SG-103, SG-209 and SG-212) on large coronary arteries were investigated in isolated canine circumflex arteries contracted with 25 mmol/l KCl or 10−7 mol/l U46619, a thromboxane A2 analogue. SG-212, SG-86, SG-209 and SG-103 were obtained by replacement of the nitroxy group of nicorandil by bromine, the hydroxy, acetoxy and nicotinoyloxy groups, respectively.Nicorandil (10−6–10−3 mol/l), SG-212 (3 × 10−4 –10−2 mol/l… 
A further study of the vasodilator and negative inotropic mechanisms of action of nicorandil and its congeners in the canine heart
It is indicated that both nicorandil and SG-209 act as K-channel openers in coronary resistance vessels and in ventricular myocardium, and that the nitroxyl and the acetoxyl group at C2 of the parent structure of nicor andil and its congeners play a pivotal role in making these compounds act asK- channel openers.
The effect of a nicorandil congener on isolated human myometrium.
Hyperpolarization induced by K+ channel openers inhibits Ca2+ influx and Ca2+ release in coronary artery
Cromakalim and Ki4032 are more specific K+ channel openers than pinacidil, nicorandil, and KRN2391 because of their inhibition of the production of IP3 and Ca2+ release from intracellular stores related to stimulation of the thromboxane A2 receptor.
Nicorandil as a nitrate, and cromakalim as a potassium channel opener, dilate isolated porcine large coronary arteries in an agonist-nonselective manner
The results indicate that the vasorelaxant actions of nicorandil and cromakalim in the porcine large coronary artery are agonist nonselective and that nicor andil exerts such an action entirely as a nitrate, whereas cromkalim does so entirely asA potassium channel opener.


Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries
In canine large epicardial coronary arteries cromakalim produced relaxation by the mechanism antagonized by glibenclamide, probably opening ATP-sensitive potassium channels, pinacidil and nicorandil did so by the mechanisms shared with cromkalim and by one not antagonizedby glibanclamide as well, and Nicorandils did so exclusively by the mode of action as a nitrate.
Effects of 2-nicotinamidoethyl nitrate (nicorandil; SG-75) and its derivative on smooth muscle cells of the canine mesenteric artery.
SG-114 possesses a stronger potency with regard to relaxation of the tissue; however, in vivo, SG-75 may have a more potent vasodilating action than SG-114, as the former inhibits neuromuscular transmission mechanisms.
Effect of 2-nicotinamidethyl nitrate (SG 75) on coronary circulation.
The results indicate that SG 75 is a potent and long-acting coronary vasodilating agent and it causes an increase in blood flow of constricted as well as non-constricted coronary artery.
Cyclic GMP as Possible Mediator of Coronary Arterial Relaxation by Nicorandil (SG‐75)
  • S. Holzmann
  • Biology
    Journal of cardiovascular pharmacology
  • 1983
Results indicate that nicorandil relaxes vascular smooth muscle, at least in part, through cGMP, which is likely to be mediated by cyclic GMP.
Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat
The results suggest that the vasorelaxant and hypotensive actions of cromakalim involve a K- channel which can be inhibited by glibenclamide, but which may be distinct from the ATP‐sensitive K+ channel of the pancreatic β‐cell.
Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels.
Cromakalim posseses a novel mechanism of vasorelaxation that is consistent with the activation of a cellular outward K+ current and was accompanied by decreases in systemic, hindquarter, mesenteric, and renal vascular resistances.
Vasodilating actions of 2-nicotinamidoethyl nitrate on porcine and guinea-pig coronary arteries.
Effects of 2-nicotinamidoethyl nitrate on smooth muscle cells of porcine and guinea-pig coronary arteries were investigated by the microelectrode and double sucrose-gap methods and from isometric contractions and suppression of the mechanical response is postulated to be mainly due to hyperpolarization of the membrane.
Relationship between relaxation and cyclic GMP formation caused by nicorandil in canine mesenteric artery
In the isolated canine mesenteric artery relaxation caused by nicorandil in the presence of noradrenaline was accompanied by a concomitant elevation of cGMP level, whilst the cAMP level was not changed by the drug.
Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite.
The hypothesis that nitrates and nitrites relax vascular smooth muscle by stimulating cyclic GMP formation is supported, similar to relaxation and guanylate cyclase activation by nitroso-containing compounds.