N-acylhydrazone derivative ameliorates monocrotaline-induced pulmonary hypertension through the modulation of adenosine AA2R activity
| Autor: | Emanuelle B. Ferraz, Carlos A. M. Fraga, Luiza V.P. Mendes, Tadeu L Montagnoli, Celso Caruso-Neves, Roberta Tesch, Allan K Alencar, Flavia E. da Silva, Lídia Moreira Lima, Gisele Zapata-Sudo, Sharlene L Pereira, Roberto T. Sudo, Valéria M.N. Cunha, José Nascimento, Carlos Mauricio R. Sant'Anna, Eliezer J. Barreiro |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Adenosine A2 Receptor Agonists Nitric Oxide Synthase Type III Receptor Adenosine A2A Hypertension Pulmonary Pulmonary Artery Enos Internal medicine Medicine Animals Rats Wistar Receptor Ultrasonography Lung Exercise Tolerance Monocrotaline biology Hypertrophy Right Ventricular business.industry Hydrazones medicine.disease biology.organism_classification Adenosine Pulmonary hypertension Phospholamban Calcium ATPase Vasodilation Blood pressure Endocrinology medicine.anatomical_structure Benzamides Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | International journal of cardiology. 173(2) |
| ISSN: | 1874-1754 |
| Popis: | Pulmonary arterial hypertension (PAH) is a disease that results in right ventricular (RV) dysfunction. While pulmonary vascular disease is the primary pathological focus, RV hypertrophy and RV dysfunction are the major determinants of prognosis in PAH. The aim of this study was to investigate the effects of (E)-N'-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), an N-acylhydrazone derivative, on the lung vasculature and RV dysfunction induced by experimental PAH.Male Wistar rats were injected with a single dose (60mg/kg, i.p.) of monocrotaline (MCT) and given LASSBio-1386 (50mg/kg, p.o.) or vehicle for 14 days. The hemodynamic, exercise capacity (EC), endothelial nitric oxide synthase (eNOS), adenosine A2A receptor (A2AR), sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB) expression, Ca(2+)-ATPase activity and vascular activity of LASSBio-1386 were evaluated.The RV systolic pressure was elevated in the PAH model and reduced from 49.6 ± 5.0 mm Hg (MCT group) to 27.2 ± 2.1 mm Hg (MCT+LASSBio-1386 group; P0.05). MCT administration also impaired the EC, increased the RV and pulmonary arteriole size, and promoted endothelial dysfunction of the pulmonary artery rings. In the PAH group, the eNOS, A2AR, SERCA2a, and PLB levels were changed compared with the control; in addition, the Ca(2+)-ATPase activity was reduced. These alterations were related with MCT-injected rats, and LASSBio-1386 had favorable effects that prevented the development of PAH. LASSBio-1386 is effective at preventing endothelial and RV dysfunction in PAH, a finding that may have important implications for ongoing clinical evaluation of A2AR agonists for the treatment of PAH. |
| Databáze: | OpenAIRE |
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