【摘 要】
：
Prolonged activation of sympathetic nerve activity is a hallmark of the pathogenesis of chronic heart failure.Current guide lines for the management of chronic heart failure recommend the suppression
【机 构】
：
Yokohama City University Graduate School of Medicine Japan
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Prolonged activation of sympathetic nerve activity is a hallmark of the pathogenesis of chronic heart failure.Current guide lines for the management of chronic heart failure recommend the suppression of sympathetic nerve activity at the level of the beta-adrenergic receptor and/or the rennin-angiotensin system.Suppression of beta-adrenergic receptor activity by beta-blockers leads to decreased activity of adenylyl cyclase,the effecter enzyme of the beta-adrenergic receptor,thereby decreases the production of cAMP,an important second messenger to regulate cardiac sympathetic activity.Because beta-adrenergic receptors are composed of three subtypes that show relatively poor tissue specificity,use of beta-blockers is contraindicated,for example,in patients with lung diseases.Adenylyl cyclase,in contrast,has nine isoforms that show distinct tissue specificity.In particular,the heart expresses type 5 adenylyl cyclase as the major isoform.Mouse with deficient expression of this isoform showed preserved basal cardiac function while they showed increased protection against various stresses,such as pressure overload or chronic catecholamine infusion,and demonstrated increased longevity.Pharmacological compounds have been developed to regulate the activity of adenylyl cyclase in an isoform dependent manner.These findings suggest the development of new strategies,beyond the current beta-adrenergic receptor blockade,in treating chronic heart failure in the future.
其他文献
Context and Objective:Thiazolidinediones (TZDs) inhibit estrogen production in ovarian cells.We explored whether TZDs affect aromatase activity.Materials & Methods:Human granulosa cells were incubated
1.Discovery of a new drug that treat insulin resistance,which is not a simple blood glucose lowering drug:We have discovered that Cyclo (his-pro) (CHP),a thyrotropin releasing hormone metabolite,stimu
This lecture will discuss the role of three mechanisms i.e.,poly(ADP-ribose) polymerase (PARP),12/15-1ipoxygenase (LO),and Na+/H+-exchanger-1 (NHE-1),in peripheral diabetic neuropathy (PDN).PARP catal
To keep blood glucose in normal level without stimulation of insulin Secretion is the effective therapy for diabetes owing to reduction of the burden for ?-cells.We found a novel diabetes-therapy base
Type 2 diabetes mellitus is associated with progressive decreases in pancreatic 8-cell function.Most patients thus require increasingly intensive treatment,including oral combination therapies followe
Dipeptidyl peptidase Ⅳ(DPPI-Ⅳ) inhibitors are emerging as a new class of therapetutic agents for the treatment of type 2 diabetes.The catalytic action of DPP-Ⅳ is the principle means of degradation of
Alzheimers disease (AD) is a neurodegenerative disorder leading to progressive loss of memory and cognitive abilities.Currently,there is no successful treatment for AD patients.In cooperation with JAD
The OBrien laboratory recently demonstrated that the expression of Heat Shock Protein 27 (HSP27) is reduced in human coronary arteries with atherosclerosis.Moreover,we showed that over-expression of H
Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme in the cardiovascular system and activated by nitric oxide (NO).Nitroglycerin as a well known drug is used for more than a century t
Background:Chronic obstructive pulmonary disease (COPD) is a major health problem and a leading cause of mortality worldwide.A Significant number of patients with COPD exhibit skeletal muscle wasting