Background: Pulmonary hypertension (PH) complicates many clinical conditions and may result in right ventricular (RV) hypertrophy and failure. Monocrotaline (MCT) induces PH by direct action on pulmonary microvasculature. Enhancement of the late sodium current (INaL) results from myocardial remodelling and may contribute to its evolution. Aims: To evaluate the effects of chronic INaL blockade in the prevention of PH-induced myocardial remodeling. Methods: PH was induced in adult rats by a single injection of MCT (60 mg/Kg i.p.); animals were studied 3 weeks later and untreated littermates served as controls. The INaL blocker ranolazine (RAN, 30 mg/Kg bid i.p.) was administered to a subset of MCT-treated rats over the 3 weeks period and completely washed-out before study. Results: MCT effects (vs control): MCT increased RV pressure. In the RV, weight, wall thickness, collagen content, myocyte electrical capacitance and cross sectional area were all increased, to indicate hypertrophy. The LV was slightly hypotrophyc instead. Nonetheless, both RV and LV myocytes showed INaL enhancement and signs of remodelling, such as α-myosin heavy chain (α-MHC) and Ito downregulation, prolonged action potential duration (APD) and delayed afterdepolarizations (DADs). IK1 was reduced in RV only. Chronic RAN effects (vs MCT alone): RAN reduced RV pressure and significantly blunted all signs of RV hypertrophy. In both RV and LV, INaL enhancement, DADs induction, α-MHC and Ito downregulation were reversed by RAN. However, APD and IK1 abnormalities persisted. Conclusions: MCT caused pressure-induced hypertrophy in the RV, but also remodelled the LV (by indirect strain?). Chronic INaL blockade prevented constitutive INaL enhancement and blunted many aspects of myocardial remodeling in both ventricles. In the RV, but not in the LV, this might partly reflect the unexpected inhibition by RAN of MCT effects on pulmonary vascular resistance.
Rocchetti, M., Rizzetto, R., Alemanni, M., Sala, L., Barile, L., Zambelli, V., et al. (2012). Prevention of myocardial remodeling by chronic INaL blockade in pulmonary hypertension. Intervento presentato a: Biophysical Society 56th annual meeting, San Diego, CA [10.1016/j.bpj.2011.11.1864].
|Citazione:||Rocchetti, M., Rizzetto, R., Alemanni, M., Sala, L., Barile, L., Zambelli, V., et al. (2012). Prevention of myocardial remodeling by chronic INaL blockade in pulmonary hypertension. Intervento presentato a: Biophysical Society 56th annual meeting, San Diego, CA [10.1016/j.bpj.2011.11.1864].|
|Tipo:||abstract + poster|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Prevention of myocardial remodeling by chronic INaL blockade in pulmonary hypertension|
|Autori:||Rocchetti, M; Rizzetto, R; Alemanni, M; Sala, L; Barile, L; Zambelli, V; Maggioni, S; Staszewsky, L; Mostacciuolo, G; Latini, R; Zaza, A|
ROCCHETTI, MARCELLA (Primo)
RIZZETTO, RICCARDO (Secondo)
MOSTACCIUOLO, GASPARE (Penultimo)
ZAZA, ANTONIO (Ultimo)
|Data di pubblicazione:||2012|
|Nome del convegno:||Biophysical Society 56th annual meeting|
|Appare nelle tipologie:||02 - Intervento a convegno|