COMPARISON OF ENDOTHELIN BINDING-SITES IN CULTURED AORTIC SMOOTH-MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS

Endothelin-1 (ET-1), which is secreted from vascular endothelial cells , is not only a potent vasoconstrictor but also a vascular smooth musc le cell growth factor. The direct effect of ET-1 on vascular smooth mu scle cells, mediated via its specific receptor may therefore play an i mportant role in hypertension and atherosclerosis. Our previous studie s indicated that ET-1 secretion from cultured aortic endothelial cells from spontaneously hypertensive rats (SHRs) at the prehypertensive st age (4 weeks old) was not significantly different from that of cells f rom age-matched Wistar-Kyoto (WKY) rats. In this study, the binding of ET-1 to cultured aortic smooth muscle cells from SHRs and WKY rats wa s studied. Using tissue explant techniques, rat aortic smooth muscle c ells from SHRs and age-matched WKY rats of different ages (4 and 24 we eks old) were successfully cultured in vitro. The maximum binding capa city (B-max) and binding affinity (K-d) of ET-1 to cultured aortic smo oth muscle cells were evaluated by a receptor-binding assay. The data revealed that the affinity of ET-1 binding to smooth muscle cells was similar in all 4 groups of experimental rats. However, the B-max of cu ltured smooth muscle cells from 24-week-old SHRs was 2.5 times higher than of smooth muscle cells from age-matched WKY rats (8.64+/-0.72 vs 3.69+/-0.10 fmol/10(6) cells) and 1.5 times higher than in aortic smoo th muscle cells from 4-week-old SHRs (8.64+/-0.72 vs 5.36+/-0.36 fmol/ 10(6) cells). These results suggest that hypertension in SHRs may be r elated to a high density of ET-1 receptors on arterial smooth muscle c ells.