RAAS抑制剂的保护作用课件.ppt

* This slide summarizes the pathophysiologic continuum that underlies the CVD continuum (which has been expanded since its inception to include other areas such as cerebrovascular disease, peripheral vascular disease, and renal disease). The pathophysiologic CV and renal continuum describes the progressive processes at the molecular and cellular levels that manifest as clinical disease. Intervention anywhere along the chain of events can modify CVD and renal disease progression. The RAAS is now understood to play a significant role in CVD pathophysiology. CV and renal continuum: RAAS as a mediator of pathophysiology * J Clin Invest. 2008 Jul;118(7):2526-34. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. Toma I, Kang JJ, Sipos A, Vargas S, Bansal E, Hanner F, Meer E, Peti-Peterdi J. Department of Physiology and Biophysics, University of Southern California, Los Angeles, California 90033, USA. Abstract Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products throu