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Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol
Author(s) -
Freitas Felipe,
Estato Vanessa,
Lessa Marcos A.,
Tibiriçá Eduardo
Publication year - 2015
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12075
Subject(s) - diltiazem , losartan , propranolol , medicine , endocrinology , saline , blood pressure , angiotensin ii , calcium
Cardiac microvascular rarefaction appears to be involved in hyperthyroidism‐induced left ventricular hypertrophy and dysfunction. We investigated the effects of losartan, an AT 1 receptor antagonist; diltiazem, a calcium channel blocker; and propranolol, a β‐adrenergic receptor antagonist, on cardiac function and structural microcirculatory cardiac alterations in an experimental model of l ‐thyroxin‐induced hyperthyroidism in rats. Hyperthyroidism ( HYPER ) was induced by intraperitoneal injections of l ‐thyroxin for 35 days (600 μg/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 isothiocyanate‐conjugated 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.