Hormonal control of renal oxygenation 1 1 Variable Responses of Regional Renal Oxygenation and Perfusion to 2 Vasoactive Agents in Awake Sheep 3

25 Vasoactive agents are used in critical care to optimize circulatory function, but their effects on 26 renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we 27 assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake 28 sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and 29 combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence 30 optode to measure tissue PO2 and a laser-Doppler probe to assess tissue perfusion. Carotid 31 arterial and renal venous cannulae enabled measurement of arterial pressure and total renal 32 oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 μg/kg/min) dose-dependently 33 reduced cortical and medullary laser Doppler flux (LDF) and PO2 without significantly 34 altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II 35 (9.8±2.1 μg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 36 18% and medullary PO2 by 38%, but did not significantly alter cortical PO2 or cortical or 37 medullary LDF. Arginine vasopressin (3.3±0.5 μg/h) caused similar decreases in RBF and 38 renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or 39 medullary LDF or PO2. Captopril had no observable effects on cortical or medullary LDF or 40 PO2, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter 41 renal oxygen consumption. We conclude that vasoactive agents have diverse effects on 42 regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, 43 RBF or total renal oxygen delivery and consumption. 44 Abstract word-count: 250 45 46