Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia.
Right ventricular hypertrophy induced by chronic hypoxia is mainly due to a mechanical stress upon the ventricular wall secondary to pulmonary arterial hypertension. However, the hypoxic chronic activation of the sympathetic nervous system can contribute to the development of right ventricular hypertrophy either via myocardial adrenergic receptors and/or a vasoconstriction and remodeling of pulmonary arteries. To highlight the specific role of the sympathetic nervous system on hypoxia-induced right ventricular hypertrophy and particularly the efficiency of carvedilol, our study compared physiological, myocardial, and pulmonary arterial morphometric data in rats treated by alpha-(prazosin), or beta-(propranolol) or alphabeta-(carvedilol) antagonist and exposed to chronic hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia, both systolic right ventricular pressure and Fulton's ratio (right/(left+septum) ventricular weight) were lower in rats treated by prazosin (-16.7 and -13.6%), propranolol (-28.6 and -12.7%) and carvedilol (-15.9 and -14.3%) respectively when compared to glucose (p<0.05). Surprisingly, prazosin was unable to reduce right ventricular hypertrophy induced by chronic hypoxia, whereas, left ventricular weight increased. Wall thickness index of pulmonary arteries increased in chronic hypoxia and was reduced by carvedilol. In conclusion, the hypoxia-induced activation of the adrenergic system participates in the development of right ventricular hypertrophy. Carvedilol is effective in reducing hypoxia-induced right ventricular hypertrophy, pulmonary arterial hypertension, and muscularization of pulmonary arteries.
Tual
L
L
Université Paris 13, Laboratoire , Résponses cellulaires et fonctionnelles à l'hypoxie, EA 2363, Association pour la Recherche en Physiologie de l'Environment, 74 rue Marcen Cachin, 93017, Bobigny, France.
Morel
O-E
OE
Favret
F
F
Fouillit
M
M
Guernier
C
C
Buvry
A
A
Germain
L
L
Dhonneur
G
G
Bernaudin
J-F
JF
Richalet
J-P
JP
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D002908:Chronic Disease; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D011224:Prazosin / Q000008:administration & dosage*; D011312:Pressure; D011412:Propanolamines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011224:Prazosin