Intrarenal renin-angiotensin system in regulation of glomerular function

The purpose of this review is to provide an update on the current knowledge regarding the role of the intrarenal rennin-angiotensin system (RAS) in the regulation of glomerular function including glomerular dynamics and filtration rate, glomerular permeability and structural alterations during chronic increases in intrarenal angiotensin (Ang) II.

Recent studies have continued to delineate the complex interactions among the various RAS components that participate in regulating glomerular function. Although Ang II acting on AT1 receptors remains as the predominant influence on glomerular dynamics, some of these effects are indirectly mediated by Ang II modulating the sensitivity of the macula densa tubuloglomerular feedback mechanism as well as the more recently described feedback mechanism from the connecting tubule. Interestingly, the actions of Ang II on these systems cause opposite effects on glomerular function demonstrating the complexities associated with the influences of Ang II on glomerular function. When chronically elevated, Ang II also stimulates and/or interacts with other factors, including reactive oxygen species, cytokines and growth factors and other hormones or paracrine agents, to elicit structural alterations.

Recent studies have provided further evidence for the presence of many components of the RAS in glomerular structures, which supports the importance of locally produced angiotensin peptides to regulate glomerular haemodynamics, filtration rate and macromolecular permeability and contribute to fibrosis and glomerular injury when inappropriately augmented.