raas系统研究的新热点_陈明(英文版).pptVIP

RAAS系统研究的新热点(The Update Of RAAS Research) 重庆医科大学附属第一医院 心内科 陈明 2009-4，广州 The hot research of RAAS Intracellular angiotensin II Ang II receptors,new agonist and antagonist ACE2 and ACE2 activator Renin and renin inhibitor RAAS and cardiac arrhythmia Brain angiotensin II Classical circulating RAAS New expanded view of RAAS RAAS:from circulation to tissue,then intrcellular intracellular angiotensin II ACE is a multifunctional enzyme equally important in the metabolism of vasodilator and antifibrotic peptides. As the membrane-bound form, ACE functions as a “receptor” that initiates intracellular signaling leading to gene expression. receptor-dependent and independent Ang II receptors Ang II Receptors: AT1 AT1: ?decrease of plasma adiponectin; ? pro-inflammatory modulation; ? increased insulin secretion ; ?β-cell apoptosis ; ? reduction of gluconeogenesis ? increased plasma triglycerides; AT2: New targets of neuronal disease? The cellular targets of the AT2 receptor in neuronal tissue are not yet clearly identified The findings on the neurotrophic actions of AT2 receptor stimulation may provide a basis for the design of new therapeutic concepts for treatment of human peripheral nerve injuries, diabetic neuropathy,neurodegenerative disorders and stroke AT2 agonist and antagonist AT2 receptor agonist :CGP 42112 AT2 receptor antagonist: Akishita et al demonstrate that the AT2 receptor antagonist PD 123319 increased neointima formation in the cuff-induced vascular injury model in mice New possible ARBs The most successful approach has been to modify AT1-selective compounds to enhance their AT2 affinity. An acylsulfonamide group, is an isosteric replacement for the tetrazole ring, to provide AT2 affinity. New compounds known as “balanced” AT1/AT2 receptor antagonists(L-162132) -equal affinity for the AT1 and AT2 Ang II