Mechanism of the vasodilating action of etozoline and its metabolites in guinea-pig aorta.
The mechanism of the vasodilating action of the diuretic etozoline and of its metabolites d- and l-ozolinone was studied in isolated aortic strips from reserpine-treated guinea-pigs. Etozoline (10 microM to 1 mM) induced a concentration-dependent inhibition of the contraction evoked by increasing K+ concentrations (15 to 45 mM) in the perfusion medium. The inhibition was of a noncompetitive type. Etozoline also inhibited contractions induced by increasing Ca++ concentrations in the perfusion medium of aortic strips depolarized by 40 mM K+. The inhibition was concentration-dependent and of a noncompetitive type. Tetraethylammonium, at concentrations reported to increase Ca++ influx into smooth muscle cells by closing K+ channels, induced contractions of aortic strips that were highly sensitive to inhibition by etozoline. Analysis of the concentration-response curves for tetraethylammonium showed that the antagonism by etozoline was of a competitive type. The pA2 value for etozoline was 5.01 +/- 0.16. Also arterial spasm, obtained by prolonging the exposure of vascular strips to tetraethylammonium (30 min), was completely suppressed by etozoline. l- and d-Ozolinone antagonized tetraethylammonium-induced contractions of aortic strips in an apparently competitive manner, but only at very high concentrations (1 and 3 mM, respectively). These results suggest that the vasodilating action of etozoline and of its metabolites is mediated by an inhibition of Ca++ influx into smooth muscle cells following a specific opening of K+ channels, but only etozoline may act through this mechanism at concentrations likely to be operative in vivo.[1]References
- Mechanism of the vasodilating action of etozoline and its metabolites in guinea-pig aorta. Dorigo, P., Belluco, P., Corradi, L., Gaion, R.M., Maragno, I. Archives internationales de pharmacodynamie et de thérapie. (1990) [Pubmed]
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