Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction: comparison of beta-caryophyllene oxide, eugenol, and nifedipine.
1. To investigate the effects of the clove oil constituents beta-caryophyllene oxide and eugenol on the heart muscle, experiments were performed on isolated papillary muscles and on ventricular myocytes of the guinea-pig. The results were compared with those obtained with the dihydropyridine, nifedipine. 2. All three substances exerted negative inotropic effects in heart muscle although with different potencies and different influences on the time course of the contraction curve. 3. They all reduced rested-state contractions (RSCs) in the presence of isoprenaline which are thought to be due to the Ca(2+) current (I(Ca)). 4. beta-Caryophyllene oxide, eugenol and nifedipine inhibited the I(Ca) in single cells from the guinea-pig ventricle in a concentration-dependent, reversible way, but with different potencies. 5. In addition to the I(Ca)-inhibiting effect, beta-caryophyllene oxide strongly inhibited and eugenol slightly inhibited the potassium current. 6. The action potential of papillary muscles at a 1 Hz contraction frequency was greatly shortened by nifedipine, slightly shortened by eugenol, but not changed by beta-caryophyllene oxide. 7. The inhibition of the potassium current by beta-caryophyllene oxide obviously prevents a shortening of the action potential due to the diminution of the I(Ca). Accordingly, the negative inotropic effect of beta-caryophyllene oxide is closely related to the inhibition of I(Ca). In contrast, eugenol and nifedipine, which shorten the action potential, exert stronger negative inotropic effects than expected from their influence on I(Ca). 8. The results show that the negative inotropic effect of a calcium channel blocker can be attenuated by an additional inhibition of potassium channels.
Sensch
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Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Str. 29, 80802 München, Germany.
Vierling
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Brandt
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Reiter
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D005054:Eugenol / Q000494:pharmacology*; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D000081223:Polycyclic Sesquiterpenes; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012717:Sesquiterpenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000081223:Polycyclic Sesquiterpenes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012717:Sesquiterpenes; D005054:Eugenol; C024714:caryophyllene; D009543:Nifedipine