Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist

R. E. Martinez, F. Stavros, I. Okun, C. Wu, F. Chen, S. Mono, R. A F Dixon, Ronald Tilton, T. A. Brock, D. L. Stacv

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

endothelins
Renal Circulation
Endothelins
Hemodynamics
hemodynamics
dyes
antagonists
Blood
Coloring Agents
blood flow
kidneys
NG-Nitroarginine Methyl Ester
Kidney
receptors
Rats
Endothelin-1
Iothalamic Acid
rats
Nitroarginine
Pentobarbital

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Martinez, R. E., Stavros, F., Okun, I., Wu, C., Chen, F., Mono, S., ... Stacv, D. L. (1996). Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist. FASEB Journal, 10(3).

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 journalArticle

Martinez, RE, Stavros, F, Okun, I, Wu, C, Chen, F, Mono, S, Dixon, RAF, Tilton, R, Brock, TA & Stacv, DL 1996, 'Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist', FASEB Journal, vol. 10, no. 3.
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. / Prevention of radiocontrast dye-induced renal hemodynamic changes using a novel endothelin-a receptor antagonist. In: FASEB Journal. 1996 ; Vol. 10, No. 3.
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