Effects of endothelin receptor A antagonist FR139317 on rats with congestive heart failure.

Abstract

AIM:

To study the effects of a selective endothelin receptor A (ETA) antagonist FR139317 on rats with congestive heart failure.

METHODS:

A congestive heart failure model was established via left coronary artery ligation in adult male Wistar rats. The rats with congestive heart failure were treated with FR139317 at two doses (1 and 5 mg . kg-1 . d-1 respectively for 6 weeks) or with vehicle. Hemodynamics, plasma level of endothelin-1 (ET-1), and mortality rate of rats were measured.

RESULTS:

Both groups treated with FR139317 (high and low dose) have lower mortality rate (25.0 % and 28.6 % vs 50.0 %) and lower plasma level of ET-1 than that of vehicle [(3.6 +/- 1.2) ng/L and (4.9 +/- 1.5) ng/L vs (5.8 +/- 1.3) ng/L]. Comparing to vehicle group, left ventricular end-diastolic pressures of the FR139317-treated groups were improved significantly [(12 +/- 6) mmHg and (14 +/- 7) mmHg vs (22 +/- 9) mmHg]. FR139317 at a higher dose reduced the mean arterial pressure of the rats with congestive heart failure and decreased the plasma concentration of endothelin to a closer level of rats with normal heart function than lower dose.

CONCLUSION:

Selective ETA antagonist FR139317 improved the hemodynamics and reduced the plasma ET-1 level and the mortality of rats with congestive heart failure

• Authors: X C Chen, X M Zhang, N S Luo, C Fang, Y M Liu, W Wu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 22 Issue 10 Pg. 896-900 (Oct 2001) ISSN: 1671-4083 [Print] United States
• PMID: 11749771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Azepines
• Endothelin Receptor Antagonists
• Endothelin-1
• Indoles
• Receptor, Endothelin A
• FR 139317

Topics

• Animals
• Azepines (pharmacology, therapeutic use)
• Endothelin Receptor Antagonists
• Endothelin-1 (blood)
• Heart Failure (drug therapy, mortality, physiopathology)
• Hemodynamics (drug effects)
• Indoles (pharmacology, therapeutic use)
• Male
• Rats
• Rats, Wistar
• Receptor, Endothelin A
• Survival Rate