Effects of antiischemic drugs on veratridine-induced hypercontracture in rat cardiac myocytes.
The effects of different groups of substances (beta-adrenoceptor antagonists, Ca2+ channel blockers and vasodilators) which are known to have antiischemic properties were studied on veratridine-induced hypercontracture. Veratridine increases Na+ influx by slowing the inactivation process of the Na+ channel, thereby inducing a continuously increased Na+ entry in depolarized cells. Veratridine (6.3 x 10(-6) M) produced a change in cell shape from rod-shape to round, resulting from hypercontracture of cells. Before treatment with veratridine the proportion of rod-shaped cells was 70% and fell to 0% 5 min after the treatment with veratridine. dl-Propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep all inhibited veratridine-induced hypercontracture dose dependently. In contrast, acebutolol, atenolol, timolol, nifedipine, diltiazem, and nitroglycerin did not inhibit the rounding of cells. Concomitantly with the rounding of cells, the [Ca2+]i was increased by veratridine. dl-Propranolol, d-propranolol and dilazep prevented the increase of [Ca2+]i induced by veratridine, whereas timolol and nitroglycerin did not. These results show that dl-propranolol, d-propranolol, l-penbutolol, d-penbutolol, nisoldipine, and dilazep possess Na+ channel blocking actions on the veratridine-modified Na+ channel, thereby preventing excessive Na+ influx and secondary Ca2+ overload.
Hashizume
H
H
Department of Pharmacology, Asahikawa Medical College, Japan.
Akiyama
K
K
Abiko
Y
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004347:Drug Interactions; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D014701:Veratridine / Q000037:antagonists & inhibitors*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015222:Sodium Channels; D014665:Vasodilator Agents; D014701:Veratridine; D016257:Fura-2