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Endothelin receptor antagonists in a beagle model of pulmonary hypertension: contribution to possible potential therapy?

AbstractOBJECTIVES:
This study investigated the pharmacologic effect of endothelin receptor antagonists on cardiopulmonary hemodynamic variables in a beagle model of pulmonary hypertension.
BACKGROUND:
We recently developed a beagle model of pulmonary hypertension that allows accurate determination of cardiopulmonary hemodynamic variables and is associated with elevated plasma endothelin-1 concentrations similar to those in pulmonary hypertension in humans.
METHODS:
Twelve beagles (pulmonary hypertension, n = 6; control group, n = 6) were studied during baseline conditions and during right atrial infusion of FR139317 (an ETA receptor antagonist), RES-701-1 (an ETB receptor antagonist), nitroglycerin and prostaglandin E1. Pulmonary hypertension was induced in experimental beagles 8 weeks after injection with 3 mg/kg body weight of dehydromonocrotaline.
RESULTS:
FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs. RES-701-1 tended to increase pulmonary artery pressure only in pulmonary hypertensive beagles. Nitroglycerin depressed pulmonary artery and systemic arterial tone equally well in control and pulmonary hypertensive animals. Prostaglandin E1 produced a greater decrease in systemic arterial pressure in pulmonary hypertensive than in normal beagles despite having the same effect on pulmonary artery pressure in both.
CONCLUSIONS:
ETA receptor antagonists decrease pulmonary artery pressure in a beagle model and may therefore be clinically useful for treatment of pulmonary hypertension.
AuthorsM Okada, C Yamashita, M Okada, K Okada
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 25 Issue 5 Pg. 1213-7 (Apr 1995) ISSN: 0735-1097 [Print] UNITED STATES
PMID7897136 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Azepines
  • Endothelin Receptor Antagonists
  • Indoles
  • Peptides, Cyclic
  • FR 139317
  • RES 701-1
  • monocrotaline pyrrole
  • Monocrotaline
  • Alprostadil
  • Nitroglycerin
Topics
  • Alprostadil (pharmacology)
  • Animals
  • Azepines (administration & dosage, pharmacology)
  • Dogs
  • Endothelin Receptor Antagonists
  • Hemodynamics (drug effects)
  • Hypertension, Pulmonary (chemically induced, drug therapy, physiopathology)
  • Indoles (administration & dosage, pharmacology)
  • Monocrotaline (analogs & derivatives)
  • Nitroglycerin (pharmacology)
  • Peptides, Cyclic (administration & dosage, pharmacology)
  • Pulmonary Circulation (drug effects)

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