1. The present study focuses on the role of endothelium on α1-adrenoceptor-mediated vasoconstriction in aorta from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). To define and quantify changes in the parameters governing agonism at α1-adrenoceptor by hypertension and/or endothelium, 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 SHR than in WKY. 3. However, in each strain of rats, removal of endothelium increased the sensitivity (P < 0.001) to phenylephrine but reduced (P < 0.05) KCl-evoked vasoconstriction, suggesting a modulation of these responses by the endothelium. The observed differences in sensitivity and maximum contraction are interpreted in terms of the operational parameters: E(m), the maximum possible effect; pK(A), the agonist affinity; α, the agonist efficacy and n, the slope for the function relating receptor occupancy to pharmacological effect. The estimated parameters reflected differences, between strains, in the signal transduction processes linked to α1-adrenoceptor stimulation ascribed 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 phenylephrine by 56.85% in SHR and by 11.80% in WKY suggesting that contracting prostanoids play a more major role in this response in SHR than in WKY. Nevertheless, these inhibitors were without effect on denuded vessels from both strains suggesting that NO and cyclooxygenase products from the media or the adventitia do not play a role on the phenylephrine-mediated responses. 5. The studied endothelial factors partially explain the observed differences in modulation of α1-adrenoceptor responses by the endothelium but suggest the participation of other compounds released by the endothelium.
|Journal||Journal of Autonomic Pharmacology|
|Publication status||Published - 26 Nov 1999|