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PMID: 2852521 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

The negative inotropic effect of nicorandil is independent of cyclic GMP changes: a comparison with pinacidil and cromakalim in canine atrial muscle.

British journal of pharmacology ·Vol. 95 ·No. 2 ·1988-10-00 ·Pages 393-8

Yanagisawa T, Hashimoto H, Taira N

Abstract

1. The negative inotropic effects of nicorandil, a nitrate with K-channel opening properties, have been compared with those of pinacidil, cromakalim and nifedipine, in canine right atrial muscle. 2. Cromakalim, pinacidil and nicorandil all produced a negative inotropic effect. However, even at their maximally effective concentrations, the force of contraction remained at about 10% of control levels, whereas contraction was abolished by nifedipine. 3. The pD2 values for the negative inotropic effects of cromakalim, pinacidil and nicorandil were 5.93, 5.37, and 4.35, respectively. 4. The negative inotropic effects of cromakalim (3 x 10(-5)M), pinacidil (3 x 10(-5) M and 3 x 10(-4) M) and nicorandil (3 x 10(-5) M) were not accompanied by changes in cyclic AMP and cyclic GMP levels, whereas that of 3 x 10(-4) M nicorandil was accompanied by an increase in cyclic GMP but not cyclic AMP concentrations. 5. The negative inotropic effect produced by 3 x 10(-4) M nicorandil was greatly reduced by 10(-2) M tetraethylammonium, whereas the increase in cyclic GMP produced by this concentration of nicorandil was not significantly changed. Sodium nitroprusside (10(-3) M) produced a large increase in cyclic GMP concentrations but had no significant negative inotropic effect. 6. It is concluded that the negative inotropic effects of nicorandil like those of cromakalim and pinacidil do not result from an increase in cyclic GMP concentrations. Instead these effects may be due to their action as K-channel openers.

MeSH Terms
Animals Anti-Arrhythmia Agents Antihypertensive Agents/pharmacology Benzopyrans/pharmacology Cromakalim Cyclic AMP/metabolism Cyclic GMP/metabolism Dogs Female Guanidines/pharmacology In Vitro Techniques Male Monoamine Oxidase Inhibitors/pharmacology Myocardial Contraction/drug effects Myocardium/metabolism Niacinamide/analogs & derivatives,pharmacology Nicorandil Nifedipine/pharmacology Pinacidil Potassium Channels/drug effects,metabolism Pyrroles/pharmacology Tetraethylammonium Compounds/pharmacology Vasodilator Agents/pharmacology
Chemicals
Anti-Arrhythmia Agents Antihypertensive Agents Benzopyrans Guanidines Monoamine Oxidase Inhibitors Potassium Channels Pyrroles Tetraethylammonium Compounds Vasodilator Agents Cromakalim Niacinamide Nicorandil Pinacidil Cyclic AMP Cyclic GMP Nifedipine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yanagisawa T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Hashimoto H
Taira N
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26 references, click to expand
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1988.tb11658.x
Published
1988-10-00
Pages
393-8
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1854162
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.1988.tb11658.x PMC Full Text View journal details
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