Contribution of the renin-angiotensin system to the control of intrarenal hemodynamics

Abstract

It must be emphasized that there remains a substantial degree of uncertainty associated with the entire question of how the RAS influences intrarenal function. On the basis of many experimental findings, it is clear that all components necessary to generate the active angiotensin peptides are present in the kidney, that there are receptors for angiotensin in various structures in the kidney and that the kidney can convert AI delivered into the renal arterial circulation. The evidence suggests that there may be significant compartmentalization of intrarenal AII formation including intravascular, interstitial, and intracellular sites. Angiotensin II converted from systemically delivered AI can elicit definitive effects to reduce RBF and GFR. From other studies, however, it is not always apparent that renal vascular resistance exhibits a close association with the activity of the RAS. Furthermore, it has not been convincingly demonstrated that under conditions of an increased renal renin content and/or renin release that there is, in fact, an increased local formation of AII occurring within the same time frame as the changes in renin content. Many conditions associated with high renin levels are not necessarily associated with renal vasoconstrictive states. Even when evidence is obtained to support an enhancement of angiotensin-dependent renal vascular resistance, it remains quite difficult to determine if the effects observed are due to increased local formation of AII or simply due to elevated circulating levels of AI and AII. Most of the observed responses to angiotensin antagonists can be explained on the basis of decreases in concentration or effectiveness of circulating angiotensin. Definitive experiments that allow a clear delineation of this issue have been difficult to design. Future studies should focus on the best means available to discriminate among the effects elicited by preformed AII, intrarenally converted AII formed from systemically delivered AI, enhanced interstitial formation of AII, or increased intracellular activation of the RAS.