Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients wi...Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125l-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes.Results L-T50 therapy improved cardiac output [CO, (2. 98±0. 31 )L/min vs (3. 24 ±0. 28) L/min, P<0. 01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93% ±9.01%, P< 0. 01), and decreased isovolumetric relaxation time (IVRT, 0.12 ±0. 04 vs 0.10 ±0. 02, P<0. 01). Serum TH levels and the maximal number of β-AR binding sites (βmax) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.展开更多
Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indi...Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease. Methods Eighty hospitalized patients （average age （59.0＋7.5） years, 46 male and 34 female） with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were： nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor Iovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or Iovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments. Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.展开更多
adrenergic receptor is the third subtype of β-adrenergic receptors. The genetic structure and pharmacological property of β 3-adrenergic receptor are markedly distinguished from β 1-and β 2-adrenergic receptor sub...adrenergic receptor is the third subtype of β-adrenergic receptors. The genetic structure and pharmacological property of β 3-adrenergic receptor are markedly distinguished from β 1-and β 2-adrenergic receptor subtypes. Recently studies show that myocardial β 3-adrenergic receptor mediates negative inotropic effect through Gi-protein/NO/cGMP pathway, the expression of β 3-adrenergic receptor and negative inotropic effect mediated by β 3-adrenergic receptor are increased in heart failure. However, because of the low expression of β 3-adrenergic receptor in the heart, the actual pathophysiological significance of β 3-adrenergic receptor remains unknown.展开更多
基金the Zhengzhou Railway Bureau Science Fund, China (99w33).
文摘Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125l-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes.Results L-T50 therapy improved cardiac output [CO, (2. 98±0. 31 )L/min vs (3. 24 ±0. 28) L/min, P<0. 01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93% ±9.01%, P< 0. 01), and decreased isovolumetric relaxation time (IVRT, 0.12 ±0. 04 vs 0.10 ±0. 02, P<0. 01). Serum TH levels and the maximal number of β-AR binding sites (βmax) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.
文摘Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease. Methods Eighty hospitalized patients （average age （59.0＋7.5） years, 46 male and 34 female） with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were： nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor Iovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or Iovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments. Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.
文摘adrenergic receptor is the third subtype of β-adrenergic receptors. The genetic structure and pharmacological property of β 3-adrenergic receptor are markedly distinguished from β 1-and β 2-adrenergic receptor subtypes. Recently studies show that myocardial β 3-adrenergic receptor mediates negative inotropic effect through Gi-protein/NO/cGMP pathway, the expression of β 3-adrenergic receptor and negative inotropic effect mediated by β 3-adrenergic receptor are increased in heart failure. However, because of the low expression of β 3-adrenergic receptor in the heart, the actual pathophysiological significance of β 3-adrenergic receptor remains unknown.
