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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 α-prazosin, or β-propranolol or αβ-carvedilol antagonist and exposed to chronic hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia, both the 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 with glucose (P < 0.05). Surprisingly, prazosin was unable to reduce right ventricle hypertrophy induced by chronic hypoxia, whereas the left ventricular weight increased. The 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 muscularisation of pulmonary arteries.

Figure 1
figure 1

Right ventricle weight according to altitude and treatment. *Hypoxia (acclimatized rats) vs normoxia; #treatment vs glucose; §carvedilol or propanolol vs prazosin. Mean ± SE, P < 0.05.

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Tual, L., Dhonneur, G. & Richalet, J. Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia. Crit Care 10 (Suppl 1), P359 (2006).

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  • Pulmonary Artery
  • Propranolol
  • Pulmonary Arterial Hypertension
  • Sympathetic Nervous System
  • Ventricular Hypertrophy