1. ¹Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
2. ²Department Pharmacology, Erasmus MC, Rotterdam, The Netherlands

Correspondence: MADH Schalekamp, c/o AHJ Danser, Department of Pharmacology, Room EE1418b, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: a.danser@erasmusmc.nl

Received 27 April 2005; Revised 23 November 2005; Accepted 12 January 2006; Published online 29 March 2006.

Abstract

Information on the levels of angiotensin II (Ang II) and its receptors in the various renal tissue compartments is still incomplete. A model is presented describing the kinetics of Ang II production, distribution, and disposal in the renal cortex. Basic features are: (1) the model is designed to derive, from Ang II measurements in blood and in whole tissue, estimates of the local densities of the Ang II type 1 (AT₁) and type 2 (AT₂) receptors, and to calculate the concentrations of endocrine and paracrine Ang II they actually 'see'; (2) glomerular and peritubular tissue are conceived as separate regions (glomerular region (Glom), peritubular region (Pt)); (3) in Glom and in Pt, Ang II is homogeneously distributed in capillary blood and in interstitial fluid; (4) the model allows for local Ang II concentration gradients between interstitium and blood; (5) Ang II from the circulation diffuses into the interstitium of Glom after convective transcapillary transport; (6) Ang II produced in tubules or Pt enters the microcirculation through diffusive overflow from interstitium; (7) the presence of cell-surface-bound Ang II depends on the reaction with AT₁ and AT₂ receptors, and the presence of intracellular Ang II depends on the internalization of Ang II – AT₁ receptor complex; and (8) the model provides for glomerular filtration, vasopeptidase-mediated degradation, and intracellular degradation as mechanisms of elimination. This model can serve as a framework for detailed quantitative studies of the renin–angiotensin system in the kidney.