Effects of hirsutine and dihydrocorynantheine on the action potentials of sino-atrial node, atrium and ventricle.
The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla MIQ. JACKSON with antihypertensive, negative chronotropic and antiarrhythmic activity, and its C3 structural epimer, dihydrocorynantheine, on membrane potentials of rabbit sino-atrial node and guinea-pig right ventricle and left atrium were studied with microelectrode techniques. In sino-atrial node preparations, hirsutine and dihydrocorynantheine (0.1 microM to 10 microM) concentration-dependently increased cycle length, decreased slope of the pacemaker depolarization (phase 4 depolarization), decreased maximum rate of rise and prolonged action potential duration. In atrial and ventricular preparations, both compounds (0.1 microM to 30 microM) concentration-dependently decreased maximum rate of rise and prolonged action potential duration. These results indicate that hirsutine and dihydrocorynantheine have direct effects on the action potential of cardiac muscle through inhibition of multiple ion channels, which may explain their negative chronotropic and antiarrhythmic activity.
Masumiya
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Saitoh
T
T
Tanaka
Y
Y
Horie
S
S
Aimi
N
N
Takayama
H
H
Tanaka
H
H
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016275:Atrial Function; D016279:Atrial Function, Left / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology; D016276:Ventricular Function; D016278:Ventricular Function, Right / Q000187:drug effects
D000470:Alkaloids; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; C038369:hirsutine