Efeitos cardiovasculares do tratamento com aceturato de diminazeno sobre a insuficiência cardíaca induzida por infarto do miocárdio em ratos normotensos e hipertensos
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2020-07-15
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Universidade Federal de Goiás
Resumo
Diminazene aceturate (Dize) is a broad spectrum antiparasitic that promotes,
among other effects, the activation of the angio tensin II converting enzyme
(ACE II). However, there are few studies that relate the use of Dize in the treatment
of myocar dial infarction (MI) and very few that relate the treatment of heart failure
(HF). Due to its activation effect of the counter regulatory axis of the Renin
Angiotensin System (RAS), it is possible that chronic treatment with Dize can
improve cardiocirculat ory function i n animals with HF MI induced . Thus, this work
sought to evaluate the performance of Dize on the cardiac and circulatory function
of normotensive (WT) and hypertensive (SHR) animals after MI. For that, males WT
and SHR of 250 300g with 12 week s of life were used. HF was induced by MI
through ligation of the left descending coronary artery. Fictitious surgeries (Sham)
were also performed to mimic the surgical stress of infarction induction. After the
MI, the period of 30 days to install the HF p icture, diagnosed by echocardiography,
was waited. Then the animals were divided into 4 groups of WT animals and 4
was waited. Then the animals were divided into 4 groups of WT animals and 4 groups of SHR animals in the respective treatments: Sham + Vehicle, Sham + groups of SHR animals in the respective treatments: Sham + Vehicle, Sham + DizeDize, , HF + Vehicle and HF + HF + Vehicle and HF + DizeDize. The treatment with . The treatment with DizeDize (10 mg /(10 mg / Kg / day; i.g.) or Kg / day; i.g.) or vehicle (water) by gavage lasted 21 days. After treatment, the animals were vehicle (water) by gavage lasted 21 days. After treatment, the animals were anesthetized and catheterized for recording and analysis of hemodynamic and anesthetized and catheterized for recording and analysis of hemodynamic and autonomic parameters in all groups. Subsequently, the animals were autonomic parameters in all groups. Subsequently, the animals were euthanized;euthanized; theirtheir hearts and thoracic aortic segments were removed for tests in isolated organ hearts and thoracic aortic segments were removed for tests in isolated organ baths. baths. Evidence showing hypertension, in the 17Evidence showing hypertension, in the 17--weekweek--old SHR model, promoting an old SHR model, promoting an increase in fibrotic cardiac content (interstitial and perivascular), hypertrophy of increase in fibrotic cardiac content (interstitial and perivascular), hypertrophy of cardiomyocytcardiomyocytes and economic and vascular activity. It reduced the contraction and es and economic and vascular activity. It reduced the contraction and effective relaxation of the heart ex vivo, vascular reactivity, parasympathetic effective relaxation of the heart ex vivo, vascular reactivity, parasympathetic cardiac activity, sensitivity and effectivcardiac activity, sensitivity and effectiveness of the baroreflex system. eness of the baroreflex system. In In normotensive animals with HF normotensive animals with HF induced by coronary ligation after 17 weeks, cardiac induced by coronary ligation after 17 weeks, cardiac remodeling with increased heart size and cardiomyocytes, fibrosis in the heart remodeling with increased heart size and cardiomyocytes, fibrosis in the heart (interstitial and perivascular) and vascular contractile capacity. He has cardiac (interstitial and perivascular) and vascular contractile capacity. He has cardiac dysfunction of the systolic type in vivo, dysfunction of the systolic type in vivo, impaired diastolic capacity ex vivo, reduced impaired diastolic capacity ex vivo, reduced vascular capacity, spontaneous baroreflex effectiveness and PAS.vascular capacity, spontaneous baroreflex effectiveness and PAS. Hypertension Hypertension associated with HF 17 weeks after coronary ligation promotes hypertrophy of the associated with HF 17 weeks after coronary ligation promotes hypertrophy of the heart and cardiomyocytes, perivascular and interstitiheart and cardiomyocytes, perivascular and interstitial fibrosis, cardiac dysfunction al fibrosis, cardiac dysfunction in vivo and ex vivo, increased contractile vascular capacity and reduced relaxing in vivo and ex vivo, increased contractile vascular capacity and reduced relaxing capacity, friendly autonomic predominance, reduced blood pressure and capacity, friendly autonomic predominance, reduced blood pressure and effectiveness of the baroreflex system and maintenance of high BP.effectiveness of the baroreflex system and maintenance of high BP. TreaTreatment with tment with the hypertension model reduces cardiac fibrosis, reduces sympathetic activity and the hypertension model reduces cardiac fibrosis, reduces sympathetic activity and improves the reflex baroreceptor. In HF, it reduces cardiac remodeling (myocyte improves the reflex baroreceptor. In HF, it reduces cardiac remodeling (myocyte and fibrosis), facilitates vascular relaxation and improves the reflex baroreceptorand fibrosis), facilitates vascular relaxation and improves the reflex baroreceptor. . In hypertension associated with HF, it is possible to reduce or remodel (myocytes In hypertension associated with HF, it is possible to reduce or remodel (myocytes and and fifibbroserosess), improve cardiac functions in the isolated organ, facilitate vascular ), improve cardiac functions in the isolated organ, facilitate vascular relaxation and improve the reflex baroreceptor.relaxation and improve the reflex baroreceptor. Together, our results demonstrate Together, our results demonstrate that tthat treatment with size can be a tool explored in cardiovascular pathologies, but it reatment with size can be a tool explored in cardiovascular pathologies, but it seems to act differently in each pathology. Finally, further studies are needed to seems to act differently in each pathology. Finally, further studies are needed to elucidate how the treatment with Dize acts on HF and hypertension, which occur elucidate how the treatment with Dize acts on HF and hypertension, which occur isolated or coisolated or concomitant.ncomitant.
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Palavras-chave
Hipertensão arterial , Cardiopatia Isquêmica , Disfunção sistólica , Fibrose cardíaca , Reatividade vascular , Sistema nervoso autônomo , Função barorreflexa , Arterial hypertension , Ischemic heart disease , Systolic dysfunction , Cardiac fibrosis , Vascular reactivity , Autonomic nervous system , Baroreflex function
Citação
LOPES, P. R. Efeitos cardiovasculares do tratamento com aceturato de diminazeno sobre a insuficiência cardíaca induzida por infarto do miocárdio em ratos normotensos e hipertensos. 2020. 184 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2020.