Article

Propranolol Diminishes Cardiac Hypertrophy But Does Not Abolish Acceleration of the Ischemic Contracture in Hyperthyroid Hearts

Department of Pharmacology, University of Athens, Goudi, Greece.
Journal of Cardiovascular Pharmacology (Impact Factor: 2.14). 10/2000; 36(3):384-9. DOI: 10.1097/00005344-200009000-00015
Source: PubMed

ABSTRACT

This study was undertaken to define the contributions of left ventricular hypertrophy (LVH) and increased adrenergic activity to the acceleration of ischemic contracture (IC) that occurs in chronic hyperthyroid rat heart. Acute and chronic hyperthyroidism (THYR) were induced by thyroxine administration for 2 and 14 days, respectively, and normal animals (NORM) served as controls. Isolated hearts were perfused in a Langendorff mode. NORM alpha acute, n = 6; THYR alpha acute, n = 8; and THYR alpha, n = 13; and NORM alpha, n = 13 were subjected to 20-min zero-flow global ischemia (I) and 45-min reperfusion (R). Additional THYR and NORM hearts treated with propranolol (prop) were subjected to 30-min I; THYR beta prop, n = 6 and NORM beta prop, n = 8, and THYR beta, n = 6, NORM beta, n = 8 served as controls. Acceleration of IC was measured by the time to peak contracture (Tmax). Left ventricular hypertrophy (LVH) was assessed by the ratio of left ventricular weight in milligrams (LVW) to animal body weight (BW) in grams. Cardiac hypertrophy developed in chronic but not acute hyperthyroidism. Propranolol reduced the extent of LVH. Contracture occurred earlier in chronic than in acute hyperthyroid and normal hearts. Propranolol did not alter contracture. In conclusion, IC is accelerated by thyroxine administration, and this is probably not due to LVH or increased beta-adrenergic activity. Propranolol diminishes LVH in hyperthyroidism.

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    • "Initially, rats were randomized into different groups: control, hyperthyroid (hyper) (T4 2.5 and T4 10.0), shamoperated (sham), and hypothyroid (hypo) treated with methimazole for 7 or 14 days. Hyperthyroidism was induced in T4 2.5 and T4 10.0 groups by daily intraperitoneal injections of T4 (2.5 and 10.0 lg/100 g body weight (BW), respectively) for 7 or 14 days [19]. T4 was dissolved using 0.04 M NaOH, and the final solution was prepared with 0.9% saline solution , pH 7.4. "
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    ABSTRACT: The effects of ATP, ADP, and adenosine in the processes of platelet aggregation, vasodilatation, and coronary flow have been known for many years. The sequential hydrolysis of ATP to adenosine by soluble nucleotidases constitutes the main system for rapid inactivation of circulating adenine nucleotides. Thyroid disorders affect a number of biological factors including adenosine levels in different fractions. Then, we intend to investigate if the soluble nucleotidases responsible for the ATP, ADP, and AMP hydrolysis are affected by variations in the thyroid hormone levels in blood serum from adult rats. Hyperthyroidism was induced by daily intraperitoneal injections of L-thyroxine (T4) (2.5 and 10.0 μg/100 g body weight, respectively) for 7 or 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water during 7 or 14 days. The treatments efficacy was confirmed by determination of hemodynamic parameters and cardiac hypertrophy evaluation. T4 treatment predominantly inhibited, and hypothyroidism (14 days after thyroidectomy) predominantly increased the ATP, ADP, and AMP hydrolysis in rat blood serum. These results suggest that both excess and deficiency of thyroid hormones can modulate the ATP diphosphohydrolase and 5'-nucleotidase activities in rat blood serum and consequently modulate the effects mediated by these enzymes and their products in vascular system.
    Full-text · Article · Jan 2011 · BioFactors
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    • "Untreated rats were used as controls and were designated as NORM. Isolated heart preparation A non-ejecting isolated rat heart preparation was perfused at constant coronary flow according to the Langendorff technique, as previously described (Pantos et al. 2000, 2002b, 2003b). In this model, coronary flow per gram of cardiac tissue was similar in all the experimental groups. "
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    ABSTRACT: The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected to zero-flow global ischaemia followed by reperfusion (I/R). Post-ischaemic recovery of left ventricular developed pressure was expressed as % of the initial value (LVDP%). Basal expression of protein kinase C epsilon (PKCepsilon) and PKCdelta and phosphorylation of p46 and p54 c-jun NH(2)-terminal kinases (JNKs) in response to I/R were assessed by Western blotting. LVDP% was found to be significantly higher in HYPO hearts than in NORM. At baseline, PKCepsilon expression was 1.4-fold more in HYPO than in NORM hearts, P<0.05, while PKCdelta was not changed. Furthermore, basal phospho-p54 and -p46 JNK levels were 2.2- and 2.6-fold more in HYPO than in NORM hearts, P<0.05. In response to I/R, in NORM hearts, phospho-p54 and -p46 JNK levels were 5.5- and 6.0-fold more as compared with the baseline values, P<0.05, while they were not significantly altered in HYPO hearts. HYPO hearts seem to display a phenotype of cardioprotection against ischaemia-reperfusion and this is associated with basal PKCepsilon overexpression and attenuated JNK activation after I/R.
    Full-text · Article · Oct 2003 · Journal of Endocrinology
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    • "In fact, thyroid hormone is shown to regulate the transcription of various myocyte-specific genes that encode important structural and regulatory proteins including myosin heavy chain isoforms and , sarcoplasmic reticulum calcium activated ATPase (SR Ca 2+ - ATPase), phospholamban, the -adrenergic receptor, adenylyl cyclase isoforms and various membrane ion channels (Klein & Ojamaa 2001). Furthermore, recent research has revealed that thyroid hormone can interfere with the regulation of important intracellular signalling transduction pathways (Fryer et al. 1998, Pantos et al. 2001, 2002a, 2003a) that are thought to be involved in protection against ischaemia-reperfusion (I/R) (Speechly-Dick et al. 1994, Kawamura et al. 1998, Zhao et al. 1998, Pantos et al. 2000, 2001, Fryer et al. 2001). In fact, chronic administration of T 4 results in changes in cardioprotective molecules such as protein kinase C (PKC) and mitogenactivated protein kinases (Fryer et al. 1998, Pantos et al. 2001, 2002a, 2003a) and this was shown to be associated with increased post-ischaemic recovery of function (Buser et al. 1990, Pantos et al. 2002a, 2003a,c). "

    Preview · Article · Sep 2003 · Journal of Endocrinology
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