Molecular and functional mechanisms of right ventricular adaptation in chronic pulmonary hypertension

Abstract

Background. Chronic pulmonary hypertension can lead to compensatory changes in the right ventricle. In this study, the adaptive mechanisms of the right ventricle in the setting of pulmonary hypertension were assessed at the molecular and functional level using a canine model of monocrotaline pyrrole–induced pulmonary hypertension.Methods. Animals underwent pulmonary artery catheterization to measure pulmonary hemodynamics before and 8 weeks after an injection of monocrotaline pyrrole, 3 mg/kg (n = 8) or placebo (n = 8) (controls). Systolic function was assessed with load-insensitive means (preload-recruitable stroke work). Myocardial biopsy specimens were collected to analyze membrane α1- and β-adrenergic receptor density and adenylate cyclase activity.Results. Eight weeks after injection, significant increases in pulmonary hemodynamic indices were noted in monocrotaline-injected dogs. Significant increases in right ventricular preload-recruitable stroke work were also observed in these animals compared with controls and occurred in association with significant increases in right ventricular α1- and β-adrenergic receptor density and isoproterenol hydrochloride–stimulated adenylate cyclase activity. No significant differences in basal adenylate cyclase activity in the right ventricle were noted between the two groups.Conclusions. These data suggest that alterations in right ventricular function in the setting of chronic pulmonary hypertension may partially be due to changes in myocardial adrenergic receptor signaling.