Abstract
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) |
|---|---|
| Journal | FASEB Journal |
| Volume | 10 |
| Issue number | 3 |
| State | Published - 1996 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology
Cite this
Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist. / Martinez, R. E.; Stavros, F.; Okun, I.; Wu, C.; Chen, F.; Mono, S.; Dixon, R. A F; Tilton, Ronald; Brock, T. A.; Stacv, D. L.
In: FASEB Journal, Vol. 10, No. 3, 1996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist
AU - Martinez, R. E.
AU - Stavros, F.
AU - Okun, I.
AU - Wu, C.
AU - Chen, F.
AU - Mono, S.
AU - Dixon, R. A F
AU - Tilton, Ronald
AU - Brock, T. A.
AU - Stacv, D. L.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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M3 - Article
VL - 10
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -