Dexfenfluramine does not worsen but moderates progression of chronic hypoxia-induced pulmonary hypertension.
This study shows for the first time, that dexfenfluramine, a 5-HT(2) receptor agonist, attenuates the development of chronic hypoxia-induced pulmonary hypertension. Chronic exposure to hypoxia, 4 weeks, induced hypoxic pulmonary hypertension in adult rat as haemodynamic and cardiac measurements showed significant modifications in right ventricle parameters (free wall right ventricle thickness; pulmonary acceleration time and velocity time integral) in chronic hypoxic control when compared to normoxic control animals. We observed that free wall right ventricle thickness and pulmonary velocity time integral were significantly less in chronic hypoxic rats treated with dexfenfluramine when compared to chronic hypoxic control rats. Similarly, rats exposed to chronic hypoxia exhibited an increase in both right ventricle pressure and weight by comparison to normoxic control animals but those variations were significantly diminished in dexfenfluramine-treated rats, indicating the moderating influence exerted by dexfenfluramine on chronic hypoxia-induced pulmonary hypertension and cardiac alterations. Thus, we report here the ability of dexfenfluramine to limit chronic hypoxia-induced pulmonary hypertension, emphasizing the importance of the time after the dexfenfluramine treatment discontinuation to assess the influence of this 5-HT receptor agonist on the development of chronic hypoxia-induced pulmonary hypertension.
Rochefort
Gaël Y
GY
LABPART - EA 3852 - IFR135 - Université François Rabelais, 10 Bd Tonnellé BP 3223, 37032 Tours Cedex 1, France.
Lemaire
Marie-Christine
MC
Eder
Véronique
V
Hanton
Gilles
G
Hyvelin
Jean-Marc
JM
Bonnet
Pierre
P
Antier
Daniel
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D020372:Dexfenfluramine / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D006349:Heart Valve Diseases / Q000209:etiology / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000473:pathology*; D008168:Lung / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018608:Ultrasonography, Doppler; D016277:Ventricular Function, Left / Q000502:physiology; D016278:Ventricular Function, Right / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D017366:Serotonin Receptor Agonists; D020372:Dexfenfluramine