Administration of radiocontrast agents increases endothelin-1 (ET-1) release and reduces renal blood flow (RBF). The current study examined the effect of a potent (IC50=3.1 nM, [ I]ET-1 binding) and highly selective (ETA/ETB=12,000) small non-peptide ETA receptor antagonist, TBC11241, on acute renal hemodynamic changes following sodium iodothalamate (SI, 5 ml/kg) infusion in the rat. Prior to infusing SI, pentobarbital-anesthetized, male Sprague-Dawley rats (350-400 g) were treated with indomethacin and L-nitroarginine methyl ester (LNAME) (10 mg/kg each) to block prostaglandin and nitric oxide formation, respectively. L-NAME increased mean arterial pressure (MAP, mm Hg) from 153 ±8 (n=9) to 165 ±3 (n=15) and reduced RBF (ml/min) from 4.0 ±0.3 to 2.0 ±0.3). Sixty min after SI infusion, values for MAP and RBF in L-NAME vs. L-NAME+SI groups were 147 ±3 vs. 151 ±3 and 1.7 ±0.3 vs. 1.0 ±0.1, respectively. TBC11241 (20 mg/kg, i.v.) prevented the Si-induced decrease in RBF (1.6 ±0.2) and induced a further fall in MAP (138 ±9). These data indicate that ETA receptors are involved predominantly in mediating decreased RBF following radiocontrast dye infusion in the rat and that highly selective ETA receptor antagonists may have therapeutic benefit.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology