Inhibitory actions of MCI-154 on guinea-pig femoral artery and vein preparations.
In guinea-pig femoral artery and vein preparations, the effects of MCI-154 were investigated on: (1) membrane depolarizations produced by 29.6 mM [K+]0 (high-K) solution and noradrenaline (NA) and on e.j.p.s produced by perivascular nerve stimulation; (2) contractions produced by NA, high-K and perivascular nerve stimulation; and, (3) endothelium-dependent relaxation produced by acetylcholine (ACh). In both femoral artery and vein preparations, MCI-154 (up to 10(-5) M) did not change the resting membrane potential or the depolarization produced by high-K. In preparations of femoral vein but not femoral artery, MCI-154 reduced NA-induced depolarization. The contractions produced by NA and high-K were reduced by MCI-154, the former more than the latter. The actions of MCI-154 were more pronounced in the vein than in the artery. The excitatory junction potential and contractions produced by perivascular nerve stimulation in guinea-pig saphenous artery preparations were inhibited by MCI-154 (greater than 10(-7) M). ACh-induced relaxations of guinea-pig femoral artery preparations precontracted with high-K were not affected by MCI-154. It was concluded that MCI-154 is an antagonist at postjunctional alpha 2-adrenoceptors, and, at high concentrations, inhibits voltage-dependent Ca2+ influx in vascular smooth muscle cells. These actions may contribute to the hypotensive effect of this drug.
Suh
S H
SH
Department of Physiology, Nagoya City University Medical School, Japan.
Chen
G
G
Xue
L
L
Zhang
G
G
Yamamoto
Y
Y
Suzuki
H
H
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D004727:Endothelium / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D005268:Femoral Vein / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011724:Pyridazines; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; C052228:MCI 154; D011188:Potassium