Modelling the changes dare to the endothelium and hypertension in the alpha-adenoreceptor-mediated responses of rat aorta

1 The present study focuses on the role of endothelium on alpha(1)-adrenoce ptor-mediated vasoconstriction in aorta from Wistar Kyoto (WKY) and spontan eously hypertensive rats (SHR). To define and quantify changes in the param eters governing agonism at alpha(1)-adrenoceptor by hypertension and/or end othelium, the operational model of analysis was used. 2 In either endothelium intact or denuded aorta, the sensitivity (P < 0.001 ) and the maximum contraction (P < 0.05) to phenylephrine were smaller in S HR than in WKY. 3 However, in each strain of rats, removal of endothelium increased the sen sitivity (P < 0.001) to phenylephrine but reduced (P < 0.05) KCl-evoke vaso constriction, suggesting a modulation of these responses by the endothelium . The observed differences in sensitivity and maximum contraction are inter preted in terms of the operational parameters: E-m, the maximum possible ef fect; pK(A), the agonist affinity; alpha, the agonist efficacy and n, the s lope for the function relating receptor occupancy to pharmacological effect The estimated parameters reflected differences, between strains, in the si gnal transduction processes linked to alpha(1)-adrenoceptor stimulation asc ribed to the presence of the endothelium. 4 N-G-nitro-L-arginine methyl ester (L-NAME), enhanced to a similar extend in both rat strains the sensitivity (P < 0.001) and the maximum contraction to phenylephrine. Indomethacin reduced the maximum contraction to phenylep hrine by 56.85% in SHR and by 11.80% in WKY suggesting that contracting pro stanoids play a more major role in this response in SHR than in WKY. Nevert heless, these inhibitors were without effect on denuded vessels from both s trains suggesting that NO and cyclooxygenase products from the media of the adventitia do not play a role on the phenylephrine-mediated responses. 5 The studied endothelial factors partially explain the observed difference s in modulation of alpha(1)-adrenoceptor responses by the endothelium but s uggest the participation of other compounds released by the endothelium.