The renal hemodynamic effects of hypertonic mannitol infusions have recently become of interest. Infusions of this 6 carbon sugar alcohol appear to have the property of preventing postoperative oliguria ( 1 ) and acute tubular necrosis in cases of crossclamping of the abdominal aorta( 2,3). Experimentally, these infusions have resulted in increased total renal blood flow in hypotensive(4,S) and normotensive(6) dogs as measured by clearance techniques, and in medullary blood flow in normotensive animals as determined by decreased dye transit time ( 7).It has been suggested (7,8,9) that mannitol infusions act by decreasing renal vascular resistance. The present study was undertaken in an attempt to determine the mechanism whereby hypertonic mannitol exerts its effect on renal vascular resistance in the in situ perfused kidney preparation.Methods. Ninety-three studies were carried out in 34 mongrel dogs (10.5-16.4 mg/ kg) of both sexes. After intravenous pentobarbital anesthesia (25 mg/kg) and positive pressure endotracheal respiration with room air were established, the left kidney was exposed through a flank incision.This kidney was perfused in situ (Fig. 1) by means of plastic tubing passing from the left carotid artery through a Sigmamotor pump into the abdominal aorta. The distal * Supported in part by grants H2987 and HE5527 from Nat. Heart Inst., U.S.P.H.S. t U.S.P.H.S. Specid Fellow HSP-17,949.part of this system was a plastic cannula tied into the aorta 2 cm below the left renal artery. The aorta was occluded just above the left kidney by means of a Potts clamp, and all lumbar vessels in the area were ligated. The only tissue perfused by this system was the left kidney. Since this pump was capable of supplying a constant flow against variations in resistance pressure from 0 to 400 mm Hg, any changes in renal vascular resistance were directly reflected in changes in pressure in the circuit. Flows were adjusted to maintain renal perfusion pressure close to control arterial blood pressure. During measurements of changes in renal vascular resistance, flow rates were not changed from control values. Pressures were measured in the brachial artery and in the perfusion tubing at a point between the Sigmamotor pump and the site of aortic cannulation. The latter pressure was taken as equivalent to renal artery pressure. Renal vascular resistance was calculated as the mean renal artery pressure (mm Hg) divided by pump flow (ml/min).Isolation of the perfusion system was confirmed in each experiment by momentarily (1-3 seconds) turning the Sigmamotor pump off and observing the fall in renal artery pressure to approximately 5 mm Hg.By means of an infusion pump, mannitol was infused directly into the renal artery as a 6.6% solution in distilled water at a rate of 1.9 ml/min.

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