Mechanisms of endothelin-induced augmentation of the electrical and mechanical activity in rat portal vein.
Actions of porcine endothelin (ET) on the electrical and mechanical activity of the rat portal vein were investigated by means of the intracellular microelectrode and isometric tension recording techniques, ET (greater than 0.1 nM) enhanced the amplitude and frequency of the spontaneous contractions which ceased in the presence of 100 nM dihydropyridine derivatives (nifedipine or nicardipine). ET (0.15 nM) increased the frequency of the spontaneous action potentials, with no change in the basal membrane potential. Higher concentrations of ET (greater than or equal to 0.3 nM) further depolarized the membrane potential and increased the spike frequency. After blocking the spontaneous action potentials with nifedipine (100 nM), ET still depolarized the membrane. The depolarization was associated with a reduction in the electrotonic potential and was blocked in a Na-deficient solution (15.5 mM) but not in Ca-free, K-deficient or Cl-deficient solutions. In a Na-deficient solution, ET still evoked action potentials without depolarization. In Ca-free solution, ET depolarized the membrane potential with small oscillations, which were blocked by nifedipine (100 nM). The results indicate that in the rat portal vein, ET enhances electrical and mechanical responses through activation of the dihydropyridine-sensitive and voltage-dependent Ca channels. Acceleration of the Ca entry induced by ET can occur with or without depolarization of the membrane and can enhance the pacemaking mechanism.
Nakao
K
K
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Inoue
Y
Y
Oike
M
M
Kitamura
K
K
Kuriyama
H
H
D000818:Animals; D001696:Biomechanical Phenomena; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D007477:Ions; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011169:Portal Vein / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D004095:Dihydropyridines; D016232:Endothelins; D007477:Ions; D010455:Peptides; D009543:Nifedipine