Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

Assessment of serum enzymatic markers of cardiomyocytes injury in female dogs submitted to ketamine S(+), atropin and xylazine association / Mensuração da atividade sérica de marcadores de lesão cardíaca em cadelas anestesiadas com cetamina S(+), atropina e xilazina

PURPOSE: To assessment of the aspartate aminotransferase (AST), creatine kinase (CK) and creatine kinase isoenzyme fraction MB (CK-MB) serum activity in female dogs anesthetized with ketamine S (+), atropine and xylazine in several associations. METHODS: Twenty three healthy female dogs randomly distributed in four groups named as GI (n=6), GII (n=6), GIII (n=6) and GIV (n=5) were treated respectively with atropine and ketamine S(+) (0.04mg/kg; 10 mg/kg); ketamine S(+) (10 mg/kg); atropine, xylazine and ketamine S(+) (0.04mg/kg; 1.1 mg/kg; 10 mg/kg) and xylazine and ketamine S(+) (1.1 mg/kg; 10 mg/kg). AST, CK and CK-MB serum activity measurement before pre-medication (M0) and one, two, three, six, 12, 24, 36 hours after. RESULTS: There was no significant change in AST, CK e CK-MB serum activity among groups. However, CK serum activity in relation to moments within the groups was increased in all groups over the time in spite of treatment, except GI. In relation to CK-MB activity, in the moments within the group, it was observed an increase compared to baseline in all groups. CONCLUSION: Creatine kinase and creatine kinase fraction MB isoenzyme showed changes in their mean values remained higher than baseline for a longer time in GIII and GIV.

OBJETIVO: Determinar a atividade sérica de AST, CK e CK-MB em cadelas anestesiadas com cetamina S (+), atropina e xilazina em diferentes associações. MÉTODOS: Vinte e três cadelas saudáveis foram distribuídas ao acaso em quarto grupos denominados GI (n=6), GII (n=6), GIII (n=6) e GIV (n=5) tratados respectivamente com atropina e cetamina S (+) (0,04mg/kg; 10 mg/kg); cetamina S (+) (10 mg/kg); atropina, xilazina e cetamina S (+) (0,04mg/kg; 1,1 mg/kg; 10 mg/kg) exilazina e cetamina S (+) (1,1 mg/kg; 10 mg/kg). A atividade sérica de AST, CK e CK-MB foi determinada antes da pré-medicação (M0) e uma, duas, três seis, 12, 24 e 36 horas após M0. RESULTADOS: Não foram encontradas mudanças significativas na atividade sérica de AST, CK e CK-MB entre grupos. Entretanto, entre momentos houve aumento da atividade sérica de CK para todos os grupos, exceto em GI.Com relação a atividade sérica de CK-MB, observou-se ao longo dos momentos aumento significativo com relação aos valores basais em ambos os grupos. CONCLUSÃO: Alterações significativas foram observadas com relação à atividade sérica de CK e CK-MB em todos os tratamentos, mantendo-se elevada por um período maior nos grupos GIII e GIV.

Focal adhesion kinase signaling in cardiac hypertrophy and failure

Focal adhesion kinase (FAK) is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival. Emerging data support a role for FAK in cardiac development, reactive hypertrophy and failure. Data reviewed here indicate that FAK plays a critical role at the cellular level in the responses of cardiomyocytes and cardiac fibroblasts to biomechanical stress and to hypertrophic agonists such as angiotensin II and endothelin. The signaling mechanisms regulated by FAK are discussed to provide insight into its role in the pathophysiology of cardiac hypertrophy and failure.