ENDOTHELIN ANTAGONISTS IN SALT-DEPENDENT HYPERTENSION ASSOCIATED WITHRENAL-INSUFFICIENCY

Bosentan is a nonspecific antagonist for endothelin (ET) receptors, an d BQ123 is a specific inhibitor for ET-A receptors. We compared the ef fects of bosentan (10 mg/kg intravenously, i.v.) and BQ123 (10 mg/kg/h i.v.) on blood pressure and renal function in deoxycorticosterone ace tate (DOCA)-salt rats, Dahl salt-sensitive (Dahl-S) rats, and normoten sive Wistar rats. In normotensive Wistar rats, bosentan and BQ123 decr eased blood pressure. Only BQ123 decreased glomerular filtration rate (GFR) and filtration fraction. These results indicate that ET-A recept ors play a role in glomerular function. In DOCA-salt rats, bosentan an d BQ123 caused a decrease in blood pressure to normal range and a decr ease in renal vascular resistances. Bosentan decreased filtration frac tion. Paradoxically, BQ123 caused a decrease in GFR. In Dahl-S rats, b osentan and BQ123 decreased blood pressure, but blood pressure did not reach normal ranges. Bosentan did not modify renal function, but BQ12 3 caused a decrease in the GFR and filtration fraction. Our results co nfirm the importance of specific and nonspecific ET antagonists in dec reasing blood pressure in models of salt-dependent hypertension. Howev er nonspecific inhibition of ET action did not improve renal function and specific inhibition of ET-A receptors by BQ123 temporarily worsene d renal function.