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CARDIAC MICROVASCULAR RAREFACTION IN HYPERTHYROID RATS IS REVERSED BY LOSARTAN, DILTIAZEM, AND PROPRANOLOL
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
Abstract
Cardiac microvascular rarefaction appears to be involved in hyperthyroidisminduced
left ventricular hypertrophy and dysfunction. We investigated the effects
of losartan, an AT1 receptor antagonist; diltiazem, a calcium channel blocker; and
propranolol, a b-adrenergic receptor antagonist, on cardiac function and structural
microcirculatory cardiac alterations in an experimental model of L-thyroxininduced
hyperthyroidism in rats. Hyperthyroidism (HYPER) was induced by intraperitoneal
injections of L-thyroxin for 35 days (600 lg/kg/day; n = 32). The
euthyroid group was treated with distilled water (EUT + VEH; n = 8). On the 14th
day, the HYPER group was divided into four groups that received an oral treatment
for 21 days with saline (HYPER + VEH; n = 8), losartan (10 mg/kg/day;
HYPER + LOS, n = 8), diltiazem (10 mg/kg/day; HYPER + DILT, n = 8), or propranolol
(10 mg/kg/day; HYPER + PROP, n = 8). An echocardiographic study was
performed at baseline, at the beginning and at the end of the pharmacological
treatment protocol (35th day). The structural capillary density in the left ventricle
(LV) was analyzed using histochemical analysis with fluorescein isothiocyanateconjugated
Griffonia simplicifolia lectin. HYPER + VEH (182 5 mmHg;
P < 0.001) presented higher systolic blood pressure (SBP) compared with
EUT + VEH (132 3 mmHg). HYPER + LOS (144 2 mmHg), HYPER + DILT
(147 3 mmHg) and HYPER + PROP (153 4 mmHg) presented lower SBP
compared with HYPER + VEH (P < 0.001). Chronic treatment with losartan,
diltiazem, and propranolol reversed cardiac structural microvascular rarefaction
(HYPER + VEH 0.16 0.01; EUT + VEH 0.35 0.02; HYPER + LOS
0.46 0.03; HYPER + DILT 0.49 0.02; HYPER + PROP 0.58 0.04 (Vv
[cap]/Vv[fib]); P < 0.001) and enhanced the LV ejection fraction of hyperthyroid
rats (HYPER + VEH 71 3; EUT + VEH 85 2; HYPER + LOS 90 3;
HYPER + DILT 85 3; HYPER + PROP 86 2%; P < 0.05). In conclusion,
chronic treatment with losartan, diltiazem, and propranolol improved the cardiac
microcirculation and function in an experimental model of hyperthyroidism in
rats.
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