Endothelin sensitivity and receptor binding in the aorta of spontaneously hypertensive rats

Endothelin is a very potent vasoconstrictor peptide secreted by endothelial cells. The aim of this study was to determine whether sensitivity to endothelin was greater in isolated aortic rings of spontaneously hypertensive rats (SHR) than in those of normotensive Wistar-Kyoto rats (WKY) and, if so, whether this was due to an increased binding affinity. Adult SHR were more sensitive to endothelin than age-matched WKY, but the maximal tension developed in response to endothelin was significantly lower in SHR than in WKY. The binding affinity of 125I-endothelin was similar in SHR [apparent dissociation constant (Kd) = 76 +/- 11 pmol/l, n = 5] and WKY (Kd = 60 +/- 10 pmol/l, n = 5). However, the density of endothelin binding sites in aortic smooth muscle cells in culture was significantly higher in WKY (2976 +/- 374 receptors per cell) than in SHR (1278 +/- 299 receptors per cell, P less than 0.01). The hyper-responsiveness of a large capacitance vessel in SHR seems relatively specific for endothelin, since the effects of norepinephrine were not significantly different between adult SHR and WKY. This hyper-responsiveness cannot be explained by an alteration in the affinity of endothelin for its receptor. However, a down-regulation of the number of binding sites could explain the lower maximal response to endothelin in SHR.