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1.
Biol Pharm Bull ; 42(6): 960-967, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30956259

RESUMO

Alamandine is a new member of the angiotensin family. Here, we studied the mRNA and protein expression of cardiac angiotensin-converting enzyme 2 (ACE2) in the chronic phase of a rat model of 2-kidney, 1-clip hypertension (2K1C), and the effects of 2-week alamandine infusion on blood pressure, cardiac indices, and ACE2 mRNA and protein expression in the hearts. The rats were subjected to to sham-operation or placement of plexiglass clips around the left renal artery. Alamandine, at a dose of 600 µg/kg/d, was administered for 2 weeks via an osmotic mini-pump. At 18 weeks, after induction of hypertension, blood pressure and cardiac indices of contractility were measured using a Powerlab Physiograph system. The ACE2 mRNA and protein levels were determined using real time-PCR and Western blotting, respectively. In the hypertensive rats, alamandine caused a significant decrease in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), left ventricular end-diastolic pressure (p < 0.001) and, left ventricular systolic pressure (p < 0.001) and increase in the maximum rate of pressure change in the left ventricle (dP/dt(max)) (p < 0.05). Also, the ACE2 mRNA expression in the heart increased in the hypertensive rats compared to the normotensive rats (p < 0.05), and alamandine restored this to normal values, although these changes were only seen at the mRNA and not the protein level. Histological analysis of cardiac tissue confirmed that alamandine decreased cardiac fibrosis and hypertrophy in 2K1C hypertensive rats. Our results indicate that alamandine, which acts as a depressor arm of the renin-angiotensin system, could be developed for treating hypertension.


Assuntos
Angiotensinas/farmacologia , Anti-Hipertensivos/administração & dosagem , Hipertensão Renovascular/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Peptidil Dipeptidase A/biossíntese , Enzima de Conversão de Angiotensina 2 , Angiotensinas/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Modelos Animais de Doenças , Hipertensão Renovascular/enzimologia , Hipertensão Renovascular/fisiopatologia , Hipertrofia/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Miocárdio/enzimologia , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
2.
Bioorg Chem ; 80: 334-346, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29986182

RESUMO

A novel Fe(III) Schiff base complex of the [FeL2(NO3)2]NO3 type where L = 2-((pyridin-4-yl)methyleneamino)-3-aminomaleonitrile was synthesized using the reflux and sonochemical methods and their antibacterial and antifungal activity were evaluated. The nanoparticles of iron oxide (Fe2O3) were obtained from the iron nano-structure complex as a precursor after calcination at 600 ˚C for 3 h. All the synthesized compounds were characterized by various spectroscopic techniques. The results of SEM showed that the morphology of iron nano-structure complex was rod-like while the morphology of the Fe2O3 nano powder was spherical. The results of the biological studies indicated that the iron nano-structure complex showed a stronger antibacterial and antifungal efficiency than its bulk complex. Finally, the empirical geometrical parameters of complexes revealed a good agreement with calculated ones at DFT-B3LYP level.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Compostos Férricos/química , Nanopartículas Metálicas/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Teoria da Densidade Funcional , Escherichia coli/efeitos dos fármacos , Fungos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Bases de Schiff/química , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática
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