Intrarenal renin-angiotensin system in renal physiology and pathophysiology

It has now been demonstrated by several techniques that all components of the renin-angiotensin system reside within the kidney. It is likely that angiotensin II is formed within interstitial renal tissue, as well as intracellularly, and acts locally in an autocrine, paracrine or intracrine manner. It has been difficult to dissect the different renal physiological roles of circulating angiotensin II as opposed to intrarenal generated angiotensin II. Angiotensin converting enzyme (ACE) inhibitors have played an important role in helping distinguish the effects of intrarenal angiotensin. Apart from hemodynamic actions and effects on glomerular filtration rate and renal tubular function, the intrarenal renin angiotensin system probably plays an important role as a regulator of renal sympathetic activity, modifies mesangial cell function, acts as a renal growth promoter, maintains endothelial cell function, and may be an important inflammatory mediator in the kidney. The renoprotective action of ACE inhibitors in reducing proteinuria and in slowing the fall in glomerular filtration rate in experimental and human renal disease may involve any of the above mechanisms. However, a prerequisite for the renoprotective action of ACE inhibitors is reduction of systemic blood pressure.