Reserpine-induced supersensitivity occurs for beta-adrenoceptor-mediated responses of heart and trachea but not of the uterus and lung

Abstract

This study was undertaken to determine whether reserpine-induced supersensitivity occurs in tissues containing beta1-adrenoceptors and in those with beta 2-adrenoceptors. Guinea-pigs and rats were pretreated with reserpine for either 3 days (5 mg kg-1 i.p. at 72 h, 3 mg kg-1 at 48 h and 3 mg kg-1 at 24 h before use) or 7 days (1 mg kg-1 daily). The sensitivities of left and right atria, papillary muscles, tracheal spirals, lung strips and uteri to isoprenaline were compared with those from untreated animals. The positive inotropic responses of left atria and papillary muscles and chronotropic responses of right atria from reserpine-pretreated animals were supersensitive to isoprenaline, the concentration-response curves being to the left. The relaxation response of the carbachol-contracted trachea also exhibited supersensitivity, but to a lesser extent. However, no supersensitivity occurred for the relaxation of carbachol-contracted lungs, K+-depolarized guinea-pig uteri or electrically stimulated rat uteri. As a pharmacological index of the presence of releasable noradrenergic stores, tyramine was added cumulatively to each tissue. Only cardiac and tracheal preparations yielded substantial responses, indicating the presence of sympathetic innervation. A relaxation of the rat uterus by tyramine was not attributable to releasable noradrenaline stores. The supersensitivity of the heart and trachea could therefore be associated with their sympathetic innervation and with the fact that their responses are mediated via beta 1-adrenoceptors; the trachea containing a small proportion of beta 1-adrenoceptors. The responses of the lung and uterus, however, are beta 2-adrenoceptor-mediated and failed to exhibit supersensitivity. Since the supersensitivity is a consequence of the neuronal depleting action of reserpine, these results are compatible with the concept that beta 1-adrenoceptors are associated with sympathetic innervation whereas beta 2-adrenoceptors are not.