Telemetry‐based Recording of Renal Cortex Oxygenation During Endogenous RAS Activation: Preliminary Observations

Abstract

Upon feeding of the food additive indole‐3‐carbinol (I3C) the liver of Cyp1A1Ren2 transgenic rats produces high levels of renin which leads to hypertension and tissue damage in the kidney. We hypothesized that endogenous RAS activation in this model would be associated with renal hypoxia. Using a new technology that enables the telemetric recording of intra‐renal tissue oxygen pressure (PO2) in conscious, free roaming animals, we here report preliminary observations on renal cortical PO2 changes during endogenous RAS activation. 1 week after implantation of the electrodes the relative change in renal cortex PO2 during bouts of 3 days of endogenous activation of RAS by feeding an 0.3% or 0.6% I3C containing diet (n=5) were recorded. 3±2 days after start of the 0.6% I3C diet, s.c. bolus infusions of valsartan/losartan (20/30 mg/kg) were administered. During 0.3% and 0.6% I3C feeding, renal PO2 levels fell to 75±7 and 63±13% from baseline values (mean±SD), with a nadir after 25±5 hours. Exogenous blockade of the angiotensin‐II receptor increased oxygen levels within 14±3 min to 98±38% of baseline values (mean±SD). These data suggest that oxygen levels in the renal cortex decrease rapidly during the onset of endogenous RAS hyperactivation. The effect is mediated by AT1‐receptor activation and may precede the known development of systemic hypertension and renal injury in this model.