Electrophysiological mechanisms of minoxidil sulfate-induced vasodilation of rabbit portal vein.
The electrophysiological and mechanical properties of the vasodilator minoxidil sulfate (MNXS) were examined in isolated smooth muscle cells and strips from rabbit portal vein. At micromolar concentrations, MNXS inhibited norepinephrine (0.1-1.0 microM)-induced contractions in isolated muscle strips. In isolated cells, norepinephrine caused a dose-dependent depolarization of the resting membrane potential, which was significantly attenuated by MNXS (5 microM); MNXS alone caused a hyperpolarization of the membrane potential. This hyperpolarization was insensitive to Na+-K+ pump blockade by ouabain, but was inhibited by the K+ channel antagonist, tetraethylammonium (20 mM). In voltage-clamp experiments, a resting (background) conductance associated with the resting membrane potential was identified. This conductance, which previously has been shown to be reduced by Ba2+ as well as tetraethylammonium, was increased by MNXS (2 microM). In additional experiments, whole-cell L-type Ca2+ currents were inhibited by micromolar concentrations of MNXS. These experiments show that concentrations of MNXS that inhibit norepinephrine-induced contractions promote K+ conductance and inhibit Ca2+ entry through voltage-dependent Ca2+ channels in vascular smooth muscle cells. These electrophysiological effects of MNXS may be responsible for the vasorelaxant effects of the drug observed in vitro and in vivo.
Leblanc
N
N
Department of Physiology, University of Nevada School of Medicine, Reno.
Wilde
D W
DW
Keef
K D
KD
Hume
J R
JR
D000818:Animals; D001696:Biomechanical Phenomena; D002469:Cell Separation; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008914:Minoxidil / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation
D013757:Tetraethylammonium Compounds; C039516:minoxidil sulfate ester; D008914:Minoxidil; D010042:Ouabain; D019789:Tetraethylammonium; D009638:Norepinephrine