Summary
An investigation has been made of the putative direct myocardial protective effects of the α1-adrenoceptor antagonists, prazosin and WB 4101, 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 56865 (0.1–10 μM) prevented tetanic contracture elicited by veratrine (100 μg/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 μM, but almost completely abolished the contractures at 100 μM. 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 μM) nor propranolol (1 μM) 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 α1-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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Correspondence to G. W. John at the above address
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Le Grand, B., Marty, A., Vieu, S. et al. Veratrine-induced tetanic contracture of the rat isolated left atrium. Naunyn-Schmiedeberg's Arch Pharmacol 348, 184–190 (1993). https://doi.org/10.1007/BF00164797
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DOI: https://doi.org/10.1007/BF00164797