VERATRINE-INDUCED TETANIC CONTRACTURE OF THE RAT ISOLATED LEFT ATRIUM - EVIDENCE FOR NOVEL DIRECT PROTECTIVE EFFECTS OF PRAZOSIN AND WB-4101

被引：12

作者：

LEGRAND, B ^{[1
]}

MARTY, A ^{[1
]}

VIEU, S ^{[1
]}

TALMANT, JM ^{[1
]}

JOHN, GW ^{[1
]}

机构：

[1] CTR RECH PIERRE FABRE, DIV CARDIOVASC DIS, 17 AVE JEAN MOULIN, F-81106 CASTRES, FRANCE

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 1993年 / 348卷 / 02期

关键词：

PRAZOSIN; WB-4101; SODIUM CHANNEL; TETANIC CONTRACTURE; VERATRINE;

D O I：

10.1007/BF00164797

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

An investigation has been made of the putative direct myocardial protective effects of the alpha1-adrenoceptor antagonists, prazosin and WB4101, against tetanic contractures of rat isolated left atria following modified Na+ channel function and consequent Ca2+ loading elicited by veratrine. Veratrine evoked concentration-dependent, reversible, tetanic contractures which were critically dependent upon the external Ca2+ concentration. Tetrodotoxin (TTX), prazosin, WB 4101 and R 56 865 (0.1-10 muM) prevented tetanic contracture elicited by veratrine (100 mug/ml) at concentrations which were significantly lower than those which decreased active tension development. The apparent Hill coefficients (nH) obtained for TTX, prazosin, WB 4101 and R 56865 were comparable (range 0.79-0.93), and are consistent with a single site of action. In contrast, the class 1 antiarrhythmic agents, quinidine and lidocaine, elicited no significant inhibition of veratrine-induced contracture at 30 muM, but almost completely abolished the contractures at 100 muM. The nH values for quinidine and lidocaine were found to be significantly greater than unity (3.1 and 2.6, respectively). The L-type Ca2+ channel blockers, diltiazem, nicardipine, nifedipine and verapamil only weakly prevented tetanic contracture, whilst markedly, and concentration-dependently, decreasing active tension development. Neither atropine (10 muM) nor propranolol (1 muM) significantly modified either veratrine-induced contractures or active tension development. In conclusion, evidence is presented of novel, direct protective effects of prazosin and WB 4101 against tetanic contracture following modified Na+ channel function and Ca2+ loading provoked by veratrine. The precise mechanisms involved are unclear at present, but appear to be distinct from blockade of atrial alpha1-adrenoceptors or L-type Ca2+ channels. A possible involvement of a TTX-sensitive, quinidine-insensitive site on, or associated with the Na+ channel is suggested.

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页码：184 / 190

页数：7