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Effects of Phosphodiesterase 5 Inhibition with Sildenafil on Atrial Contractile and Secretory Function
The Korean Journal of Physiology and Pharmacology ; : 149-154, 2006.
Artículo en Inglés | WPRIM | ID: wpr-728565
ABSTRACT
Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-1, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, 2.84+/-1.71%, n=12, vs -0.71+/-0.86%, n=21; p<0.05) and decreased ANP release (-9.02+/-3.36%, n=14, vs 1.35+/-3.25%, n=23; p<0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Volumen Sistólico / Donantes de Tejidos / Presión Sanguínea / Factor Natriurético Atrial / Péptido Natriurético Tipo-C / Líquido Extracelular / Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 / Citrato de Sildenafil / Guanilato Ciclasa Límite: Humanos Idioma: Inglés Revista: The Korean Journal of Physiology and Pharmacology Año: 2006 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Volumen Sistólico / Donantes de Tejidos / Presión Sanguínea / Factor Natriurético Atrial / Péptido Natriurético Tipo-C / Líquido Extracelular / Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 / Citrato de Sildenafil / Guanilato Ciclasa Límite: Humanos Idioma: Inglés Revista: The Korean Journal of Physiology and Pharmacology Año: 2006 Tipo del documento: Artículo