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1.
Int J Med Sci ; 17(16): 2594-2602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029102

RESUMO

Pulmonary hypertension (PH) is a lethal and rapidly progressing disorder if left untreated, but there is still no definitive therapy. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism underlying PH. Among the vasomediators of the pulmonary circulation is the renin-angiotensin system (RAS), the involvement of which in the development of PH has been proposed. Within the RAS, angiotensin-converting enzyme 2 (ACE2), which converts angiotensin (Ang) II into Ang-(1-7), is an important regulator of blood pressure, and has been implicated in cardiovascular disease and PH. In this study, we investigated the effects of the ACE2 activator diminazene aceturate (DIZE) on the development of PH secondary to left ventricular dysfunction. A model of PH secondary to left ventricular dysfunction was established in 6-week-old Wistar rats by ascending aortic banding for 42 days. The hemodynamics and pulmonary expression of ACE, Ang II, ACE2, Ang-(1-7), and the Ang-(1-7) MAS receptor were investigated in the early treatment group, which was administered DIZE (15 mg/kg/day) from days 1 to 42, and in the late treatment group, administered DIZE (15 mg/kg/day) from days 29 to 42. Sham-operated rats served as controls. DIZE ameliorated mean pulmonary artery pressure, pulmonary arteriolar remodeling, and plasma brain natriuretic peptide levels, in addition to reversing the overexpression of ACE and up-regulation of both Ang-(1-7) and MAS, in the early and late treatment groups. DIZE has therapeutic potential for preventing the development of PH secondary to left ventricular dysfunction through ACEII activation and the positive feedback of ANG-(1-7) on the MAS receptor. A translational study in humans is needed to substantiate these findings.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Diminazena/análogos & derivados , Ativadores de Enzimas/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Disfunção Ventricular Esquerda/complicações , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Diminazena/farmacologia , Diminazena/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ativadores de Enzimas/uso terapêutico , Humanos , Hipertensão Pulmonar/etiologia , Fragmentos de Peptídeos/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico
2.
Kaohsiung J Med Sci ; 23(4): 207-10, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17395571

RESUMO

Volvulus of the colon is an unusual cause of intestinal obstruction in the pediatric population. Splenic flexure colonic volvulus is the most uncommon site in children. We report a case of splenic flexure volvulus (SFV) in a 21-month-old boy with underlying cerebral palsy and epilepsy. He experienced abdominal distension, bilious vomiting and absence of bowel movement for 2 days. Abdominal radiography showed a proximal distended colon and a "coffee bean sign" at the left upper quadrant. Barium enema revealed a "bird beak sign" at the splenic flexure, which confirmed the diagnosis of SFV. Detorsion of SFV occurred while undergoing exploratory laparotomy. He received regular follow-up in the subsequent 3 years without recurrence.


Assuntos
Colo Transverso , Doenças do Colo/cirurgia , Volvo Intestinal/cirurgia , Doenças do Colo/diagnóstico , Humanos , Lactente , Volvo Intestinal/diagnóstico , Masculino
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