Effects of Hypertonic Mannitol on Renal Vascular Resistance.

Abstract

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.

Effect of Mannitol on Glomerular Ultrafiltration in the Hydropenic Rat

“…Most investigators have favored an increase in either or both rpf and PG as the major factors contributing to this beneficial effect. The postulated changes were attributed to a vasodilating effect of mannitol upon the AR vessels (11)(12)(13).…”

“…The widespread use of mannitol in clinical medicine in an effort to increase, maintain, or restore glomerular filtration rate has inspired a large number of studies which have examined the mechanism of action of this useful agent (1)(2)(3)(4)(5)(6)(11)(12)(13)(14). Most investigators have favored an increase in either or both rpf and PG as the major factors contributing to this beneficial effect.…”

“…Previous studies examining the mechanism of action of osmotically active agents favor the first two explanations, increased plasma flow and increased AP, both of which could be mediated by a reduction in afferent arteriolar resistance (AR) (3,(11)(12)(13)(14). However, mannitol appears more effective in restoring glomerular filtration than other agents which possess the capacity to vasodilate the renal vasculature (13), and this 1 Abbreviations used in this paper: AR, afferent arteriolar resistance (mm Hg/nl/min/g kidney wt); C, protein concentration; CA, systemic protein concentration; CE, efferent pertibular capillary protein concentration; AIP, hydrostatic pressure gradient across glomerular capillary (AP = PG -Pt) ( 7rA, systemic oncotic pressure; QO, rpf, nephron plasma flow (nl/min/g kidney wt); snbf, single nephron blood flow; snff, superficial nephron filtration fraction; sngfr, nephron filtration rate (nl/min/g kidney wt); x*, normalized glomerular capillary length (dimensionless parameter).…”

The Role of Cell Swelling in Ischemic Renal Damage and the Protective Effect of Hypertonic Solute

“…Furthermore, the larger vessels of ischemic kidneys treated with mannitol had a mean endothelial thickness which was even less than that of normal vessels of the same size (0.45 ±0.04 and 0.57 -'0.04 / mean thickness, respectively with P of the difference <0.05). This reduction in endothelial thickness hypertonic mannitol even into nonischemic tissues (22)(23)(24)(25)(26)(27).…”

Restoration and maintenance of glomerular filtration by mannitol during hypoperfusion of the kidney

“…Our data demonstrate conclusively that this suggestion is correct. A number of investigators have found that mannitol (20)(21)(22)(23) and other hypertonic solutions (24) can increase renal blood flow and decrease renal vascular resistance in the normal dog kidney. It seems plausible that renal vascular resistance is increased in the hypoperfused rat kidney, perhaps at the afferent arterioles.…”