Nifedipine and nisoldipine modulate membrane potential of vascular endothelium via a myo-endothelial pathway.
Effects of nifedipine (Nif) and nisoldipine (Nis), dihydropyridine Ca2+ channel blockers (DHPs) on membrane potential and currents of endothelial cells, which are enzymatically dispersed (dis-ECs) from or exist in arterial segments (seg-ECs) of rabbit and rat aorta, were examined. Outward currents induced by 1-10 microM acetylcholine (ACh) in dis-ECs were neither affected by a receptor operated Ca2+ channel blocker, SK&F 96365 (SKF), nor DHPs. ACh hyperpolarized dis-ECs and seg-ECs by 15-20 mV, whereas phenylephrine (Phe) elicited oscillatory depolarization in seg-ECs but not in dis-ECs. The Phe-induced response in seg-ECs was significantly inhibited by treatment with 18beta-glycyrrhetinic acid, a disrupter of gap junctions. Application of 0.3 microM Nif or Nis effectively inhibited the Phe-induced oscillatory depolarization, while these DHPs did not affect ACh-induced hyperpolarization in seg-ECs. The lack of effect on dis-ECs indicates that DHPs have little effect on dis-ECs themselves, nevertheless DHPs inhibit the Phe-induced endothelial potential oscillation which is conducted from smooth muscle cells via a myo-endothelial pathway.
Muraki
K
K
Department of Molecular and Cellular Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. kmuraki@phar.nagoya-cu.ac.jp
Watanabe
M
M
Imaizumi
Y
Y
D000818:Animals; D001011:Aorta; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015737:Nisoldipine; D009543:Nifedipine