USE OF THE OPERATIONAL MODEL OF AGONISM AND [H-3] PRAZOSIN BINDING TOASSESS ALTERED RESPONSIVENESS OF ALPHA(1)-ADRENOCEPTORS IN THE VAS-DEFERENS OF SPONTANEOUSLY HYPERTENSIVE RAT

Changes in functional responsiveness to alpha(1)-adrenoceptor activati on with noradrenaline and in [H-3]prazosin binding in the epididymal p ortion of vas deferens from normotensive Wistar Kyoto (WKY) and sponta neously hypertensive rats (SHR) were investigated. The operational mod el fitting and the nested hyperbolic method were used to analyze the e ffects of irreversible receptor alkylation by phenoxybenzamine (0.1 mu M) on the alpha(1)-adrenoceptor mediated contractile responses to nor adrenaline of vasa deferentia from SHR and WKY rats. Saturation isothe rms for [H-3]prazosin revealed a significant increase (P < 0.05) in th e B-max in SHR vas deferens (145 +/- 19 fmol/mg protein) compared with vas deferens from normotensive controls (75 +/- 12 fmol/mg protein) w ithout changes in the K-D. No differences in the proportion of high an d low affinity binding sites for WB-4101 and 5-methylurapidil were obs erved. The maximum contractile response, alpha, (P < 0.001) and the pE C(50) (P < 0.05) values for noradrenaline were greater for SHR than fo r WKY rat tissues. The apparent affinity (pK(A)) determined by the nes ted hyperbolic method and by the operational model of agonism was foun d to be similar in the two strains. In agreement with relative pEC(50) , the efficacy (tau) value for SHR was greater than for WKY rats. Howe ver, the difference in the tau estimates did not reach statistical sig nificance. In summary, in the epididymal portion of SHR vas deferens, the increased maximum contractile response to noradrenaline is due to an increase of E-m. Taken together, the tau values and the results fro m binding experiments lead to the assumption that the transducer const ant K-E must be greater in SHR than in WKY rats, suggesting a deterior ation in the transduction of the stimulus provided by the agonist in h ypertensive animals.