Intrarenal Blockade of Angiotensin II AT1 Receptor Abolishes Renal Cortical Hypoxia in Salt Restricted Animals

Abstract

Low salt (LS) diet results in activation of the renin‐angiotensin system (RAS) to maintain volemia and arterial blood pressure. We hypothesized that LS‐induced RAS activation increases Na+ transport in the kidney contributing to hypoxia also in the otherwise healthy kidney since renal blood flow (RBF) is not under metabolic control.Male Sprague Dawley rats were fed normal (NS, 0.4%) or low (LS, 0.01%) salt diet during two weeks. Thereafter, catheters were placed in the carotid artery and femoral vein for blood pressure measurement and infusion of saline containing 3H‐inulin, respectively, in anesthetized (thiobutabarbital) animals. The left kidney was immobilized and a catheter was placed in the renal artery. Measurements were obtained during a baseline and after infusion of the angiotensin II AT1‐receptor blocker candesartan (4.2 µg/kg) directly into the renal artery. Oxygen consumption (QO2) was estimated from the arterio‐venous difference in O2 content multiplied by RBF (Transonic flow probe). Renal cortical and medullary partial pressures of oxygen (PO2) were measured using Clark‐type electrodes. Mean arterial blood pressure, glomerular filtration rate and RBF were similar in both groups. The LS rats had less efficient Na+ transport along with higher QO2 compared to NS. LS reduced cortical PO2 whereas medullary PO2 was increased compared to NS. Importantly, acute AT1‐receptor inhibition by candesartan normalized cortical PO2 and restored the cortico‐medullary oxygen gradient in the animal receiving LS.These results indicate that LS‐induced cortical hypoxia is associated with angiotensin II AT1 receptor activation, which induces hypoxia in the kidney cortex.