Interstitial fluid volume: local regulatory mechanisms.
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Biomedical subjects
Publications and source records attributed to K Aukland.
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While 15 mu microspheres (Ms) in principle provide a measure of glomerular flow, uptake rate of inert diffusible tracers indicates "effective" or "nutrient" flow, i.e. essentially postglomerular capillary flow. Paired measurements of glomerular and postglomerular flow were made in tissue samples from outer, middle and inner cortex (C1, C2, C3) and medullary zones. After a control Ms injection, renal vascular conductance (RVC) was altered in one kidney whereupon a second Ms injection was made, immediately followed by infusion of the 125I-iodoantipyrine and tritiated water. RVC was increased maximally by i.a. infusion of acetylcholine with and without reduced renal arterial pressure, whereas moderate vasodilation was produced by lowering renal arterial or rising ureteral pressure. RVC was reduced by i.a. or i.v. infusion of angiotensin II. Within a mean RVC range of 50 to 180% of control the fractional distribution of zonal postglomerular flow remained unaltered, in agreement with previous results obtained from local H2 gas desaturation rate. Glomerular flow was about 20% higher in C1, equal in C2 and 40% lower in C3 as compared to postglomerular flow in control kidneys. This disparity nearly disappeared during maximal vasodilation and tended to increase during vasoconstriction. The results might suggest a variable net postglomerular effective flow in radial direction through the renal cortex. Alternatively, the fractional redistribution of Ms might reflect a variable degree of Ms skimming at the afferent arteriolar inlets along the interlobular arteries.
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The tissue/blood partition coefficient, lambda tb, defined as the amount of blood having the same tracer content as one unit of tissue at diffusion equilibrium, was determined for 125I-iodoantipyrine (I-Ap) and tritiated water (THO) in the dog kidney cortex. Measurements were made after in vivo equilibration for 75 to 300 s and with liver circulation excluded. In 18 kidneys, lambda tb for I-Ap averaged 1.38 (S.D. 0.13) w/w (weight/weight), without significant correlation to hematocrit (range: 23-43) or to urine pH (range 5.5-8.6). The lambda tb for THO averaged 0.97 (S.D. 0.06) v/w (volume/weight), close to the relative water contents. Erythrocyte/plasma partition for I-Ap was 0.82 w/w, compared to a water partition of 0.72. Thus, at diffusion equilibrium the apparent I-Ap concentration in renal cortical and red cell water exceeds that of plasma water by 14 and 60%, respectively. It follows that I-Ap cannot be used as a general indicator for total tissue water content. When used for measurement of local blood flow and modum Kety, lambda tb must be determined for each tissue and species.
Disparate reports on intrarenal blood flow distribution prompted a direct comparison between microspheres (Ms) and inert diffusible tracers (DT). The "tissue sampling technique" for estimating local flow with DT (Kety) was adapted for the dog kidney, using 125I-iodoantipyrine (1-Ap) and tritiated water (THO). Ms (15 micron) were injected 2-3 min prior to 10-15 s DT infusion made during continuous 1 s arterial blood sampling. Tracers were measured in 7 to 20 samples from each of the following zones: Outer, middle and inner cortex (C1, C2, C3), outer and inner halves of outer medulla (OM1, OM2), and inner medulla (IM). I-Ap and THO gave closely similar flow distribution, and average total renal blood flow (RBF) of 3.90 and 3.78 as compared to 3.94 ml/min . g with Ms. Flow in C2 (ml/min . g) was similar with all tracers, and in per cent thereof average local flows were: C1 102, C3 70, OM1 34, OM2 12, and IM 2 with DT versus 117, 53, 12, 3, and 0 with Ms. Zonal flow fractions of total RBF obtained with DT were: C1 0.41, C2 0.33, and C3+medulla 0.26 versus 0.51, 0.33 and 0.16 with Ms. Thus, a Ms surplus in C1 relative to DT flow, representing 10% of total RBF, matched a Ms deficit in C3+medulla. This disparity might result from: (1) Failure of Ms to enter deep afferent arterioles in proportion to blood flow, (2) diffusion of DT from deep portions of the interlobular arteries, and/or (3) postglomerular inward flow of blood and DT.
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A new technique has been developed to make deep renal cortical structures in rats accessible for micropuncture: The left kidney is dissected free and immobilized in a lucite cup. A lense-shaped slice, 1--2 mm thick and about 5 x 5 mm wide, is cut off from the dorsal aspect of the kidney. Blood oozing from the cut surface is removed by flushing with saline and suction by microsponges. The bleeding stops in 1--3 min and causes none or only transient fall in arterial pressure (PA). Up to 40 glomeruli become visible and remain circulated for several hours, as shown by injection of dye or silicone rubber. Glomerular capillary pressures (PG), measured with servocontrolled counter pressure (Wiederhielm), showed no consistent change with time and no correlation to PA. Average PG +/- S.E. in mmHg (number of glomeruli in parentheses) were: Wistar rats (WR), Inactin anesthesia, 57.8 +/- 1.4 (41), Membumal anesthesia, 58.1 +/- 1.3 (13). Sprague Dawley rats, Inactin, 58.1 +/- 1.7 (14). In WR, PG was lower in deep than in midcortical glomeruli: less than or equal to 0.4 mm below kidney surface, 57.9 +/- 1.8 (20); 0.5--0.9 mm: 60.5 +/- 1.5 (20) and greater than or equal to 1.0 mm: 53.8 +/- 2.5 (13). Pressure in Bowman's capsule: 11.2 +/- 0.6 (30). The observed PG is higher than previously reported on the Munich mutant strain of WR, and suggests that glomerular filtration equilibrium is not reached.
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Tetracycline hydrochloride (TC), 30-70 mg/kg infused intravenously in dogs in the course of a few minutes, reduced clearance of inulin (Cin) and p-aminohippuric acid (CPAH) on an average to less than 5% of control. In spite of increased intrarenal pressure (approximately 50 mm Hg), electromagnetically recorded renal blood flow was preserved, indicating that the reduction of Cin and CPAH resulted from tubular obstruction, not renal vasoconstriction. The metabolic rate of the cortex and outer medulla fell to 69% of control after TC, as measured by the heat accumulation rate. Further reduction to basal metabolic level (30% of control) was reversibly produced by elevating ureteral pressure, suggesting that the high metabolic rate was caused by continued active reabsorption of sodium chloride at about half the control rate. Thus Cin greatly underestimated glomerular filtration rate in the TC-damaged kidney. From these results and the observation of TC-containing casts in the medullary tubules, we conclude that TC caused tubular obstruction and that leakage of inulin and PAH from the tubules occurred mainly distally to the major sodium-reabsorbing tubular segments.