Positive inotropic effects of imidazoline derivatives are not mediated via imidazoline binding sites but alpha1-adrenergic receptors.

摘要: Imidazoline-binding sites are non-adrenergic receptors and classified into I11/I2 subtypes. There is strong evidence that I1-binding sites, located in the rostro-ventrolateral medulla, involved regulation of blood pressure. However, less known about peripheral participation cardiovascular reactions. Therefore, aim this study was to investigate whether specific imidazoline derivatives influence myocardial contractility binding expressed rat heart. Agmatine, clonidine idazoxan failed alter inotropy left atria within whole concentration range tested (1 nM - 100 microM), whereas cirazoline (1- microM) moxonidine (100 increase by 20-30%. After preincubation with alpha1-adrenoceptor antagonist prazosin, stimulated antagonized, indicating more an alpha1-adrenergic site mediated mechanism. Radioligand-binding studies membranes ventricles using [3H]-clonidine specify yielded KD values 12.7 microM, confirming functional results absence rats. existence low affinity I2-binding determined [3H]-idazoxan labeling could not be excluded since a 0.5 microM calculated competition guanabenz (Ki = 0.1 58.1 129 confirmed specificity I2-binding.