Cardiovascular effects of lepadiformine, an alkaloid isolated from the ascidians Clavelina lepadiformis (Müller) and C. moluccensis (Sluiter).
The effects of lepadiformine, a natural marine alkaloid isolated from the ascidians Clavelina lepadiformis (Müller) and C. moluccensis (Sluiter), were studied in vivo by arterial blood pressure (aBP) recordings and electrocardiograms (ECG) in anaesthetised rats and in situ by peripheral vascular pressure recordings on perfused rabbit ear. Transmembrane resting (RP) and action (AP) potentials were also recorded by intracellular microelectrodes on electrically stimulated left ventricular papillary muscle and spontaneously beating atrium isolated from rat and frog hearts, respectively. Intravenous injection of lepadiformine (6mg/kg) produced marked bradycardia and a lengthening of ECG intervals as well as a transient decrease of aBP, which rapidly returned to normal. The decrease of aBP may have been related to a vasoconstrictor effect observed in the perfused ear experiment. Lepadiformine did not alter RP, but significantly lengthened the repolarising phase of AP in rat papillary muscle and frog atrium. Lepadiformine also mimicked the effect of Ba(2+) (0.2mM) on the rat AP repolarising phase. Moreover, the lengthening of the AP in frog atrium induced by lepadiformine still developed after the delayed outward K(+) current (I(K)) was blocked by tetraethylammonium (10mM). These observations suggest that lepadiformine-induced lengthening of AP duration was not due to a decrease of I(K), but may reasonably be attributed to a reduction of the inward rectifying K(+) current (I(K1)). This blockade of I(K1) could account for the cardiovascular effects of lepadiformine in vivo and in vitro and suggests that lepadiformine has antiarrhythmic properties.
Jugé
M
M
Département de Pharmacologie, Faculté de Pharmacie, BP 53508, 44035 Cédex 1, Nantes, France.
Grimaud
N
N
Biard
J F
JF
Sauviat
M P
MP
Nabil
M
M
Verbist
J F
JF
Petit
J Y
JY
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014561:Urochordata / Q000737:chemistry*
D000470:Alkaloids; D015221:Potassium Channels; C431548:lepadiformine