American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Aug 2017
Luminal ANG II is internalized as a complex with AT1R/AT2R heterodimers to target endoplasmic reticulum in LLC-PK1 cells.
ANG II has many biological effects in renal physiology, particularly in Ca2+ handling in the regulation of fluid and solute reabsorption. It involves the systemic endocrine renin-angiotensin system (RAS), but tissue and intracrine ANG II are also known. We have shown that ANG II induces heterodimerization of its AT1 and AT2 receptors (AT1R and AT2R) to stimulate sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity. ⋯ This result was confirmed by an increase of β-arrestin phosphorylation after ANG II treatment, clathrin-mediated endocytosis being dependent on dephosphorylation of β-arrestin. Internalized ANG II colocalized with an endoplasmic reticulum (ER) marker and increased levels of AT1R, AT2R, and PKCα in ER-enriched membrane fractions. This novel evidence suggests the internalization of an ANG II-AT1/AT2 complex to target ER, where it might trigger intracellular Ca2+ responses.
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Am. J. Physiol. Renal Physiol. · Aug 2017
Comparative StudyAccounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.
We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. ⋯ We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo2 The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (V̇o2) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo2 to the major the determinants of [Formula: see text] and V̇o2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.