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Recent studies indicate that intrarenal distribution of blood flow measured with microspheres (Ms) during control conditions depends on Ms size. We therefore compared local flow in outer and middle cortex (C1 and C2) and inner cortex plus the medulla (C3M) using 10.5-12.0 and 13.9-15.0 mum Ms (Ms 10 and Ms 15). One pair of Ms 10 and Ms 15 was injected during control and a second pair at 80% increased or 50% decreased total renal vascular conductance (RVC), as induced by infusion of acetylcholine (Ach) and angiotensin II (Ang) or noradrenaline (NA). All zones participated in dilation and constriction, as indicated by both Ms sizes. Ms 15 underestimated C3M flow as compared to Ms 10, by 19% during control or Ang, and by 3% during Ach (P less than 0.02). The C3M flow fractions increased during Ach and decreased during Ang, whereas NA gave greatly variable results, on average no change. Renal Ms extraction averaged 97.0 +/- 3% for Ms 10, 98.6 +/- 2.4% (S.D.) for Ms 15. About 8% of Ms 10 and less than 1% of Ms 15 were located in peritubular capillaries in each cortical zone. Neither total Ms extraction nor zonal extraglomerular Ms fraction changed over the present RVC range. Thus, the Ms 10 to Ms 15 differences as well as the observed redistribution must be due to differences in local entry of Ms into the afferent arterioles. However, steric restriction of Ms at arteriolar inlets did not play a significant role. The measured redistribution of fractional flow could in part be due to skimming of Ms at arteriolar inlets along the interlobular arteries (i.l.a.), depending on the C3M flow fraction, Ms size and i.l.a. diameter. If the observed fractional flow redistributions were solely due to variable Ms skimming, Ms 15 underestimated C3M flow by 53%, Ms 10 by 43%, during Ang as compared to Ach. Although Ms 10 and Ms 15 may correctly indicate the direction of fractional glomerular flow redistribution, at least Ms 15 overestimates this phenomenon quantitatively.

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.

The effect of angiotensin-II on the local renal blood flow and arterial blood pressure was investigated in the rat with the H2 gas washout technique. Increasing intravenous infusion rates gave a decreasing blood flow and increasing blood pressure, renal vascular resistance being close to proportional to the log of infusion rate. In kidneys with experimental neoplasm, the flow reduction was proportionally less in the tumor than in intact renal tissue. The respective flow levels were maintained for 10 to 45 min without tendency to change.

Renal blood flow (RBF) is markedly reduced in kidneys with unilateral ureteral obstruction (UUO), possibly due to vascular constriction. Whether obstructive nephropathy is associated with impaired RBF autoregulation is unknown. We therefore investigated RBF autoregulation in obstructed and contralateral unobstructed rat kidneys during and following release of 24 h and 6 days of UUO, using stepwise reduction of renal arterial pressure and electromagnetic recording of RBF. The lower pressure limit of autoregulation was increased and the maximal vasodilatory ability in response to infusion of acetylcholine into the renal artery was reduced only in the unobstructed kidney at 24 h of UUO. Thus, we conclude that the vasodilatory reactions to both these maneuvres, previously observed to be markedly reduced during acutely elevated ureteral pressure (Hope & Clausen 1982), were reestablished: In the obstructed kidneys in less than 24 h (RBF approximately 70% of control) and in the contralateral unobstructed kidneys in less than 6 days (RBF approximately 140% of control). Infusion of the thromboxane A2 (TXA) synthetase inhibitors imidazole and 3-ethyl pyridine in controls and at 24 h and 6 days of UUO did not produce renal vasodilation. These results do not support the suggestion that TXA contributes directly to the increase in renal vascular resistance observed during or following release of UUO in the rat.

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.

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.

Simultaneous measurement of glomerular flow by 15 mum microspheres (Ms) and postglomerular capillary flow by 125I-iodoantipyrine (I-Ap) suggest that about 10% of total RBF flow inward through the entire cortex in the postglomerular capillaries of the dog kidney. This flow fraction might be variable (Clausen et al. 1978, 1980) and perhaps even reversible. To test this possibility we injected 50 mum Ms into the renal artery in order to obstruct interlobular arteries and produce a selective reduction of outer cortical glomerular blood flow and postglomerular pressure. The 50 mum Ms reduced total RBF by 50%. In the outer cortex, postglomerular flow measured by I-Ap was significantly less reduced than glomerular flow as measured by 15 mum Ms: Whereas the inward flow fraction from inner cortex to the medulla was maintained, about 5% of RBF now drained from midcortex to outer cortex. This observation support the theory of a variable net postglomerular capillary flow of radial direction in the cortex of the dog kidney.

Discrepancies concerning the lower pressure limit of renal blood flow (RBF) autoregulation, different autoregulatory adjustments in deep and superficial renal zones and dissociation of RBF and filtrate production stimulated the present study. Autoregulation of renal blood flow was investigated at reduced renal arterial blood pressure (RAP) in Sprague-Dawley rats using 4 different flow methods: uptake of 125I-iodoantipyrine (I-Ap) and 86Rb, local detection of hydrogen gas washout rate (H2) and, in the autoperfused kidney, electromagnetic flowmetry (FM). With I-Ap and 86Rb, RBF was maintained at a RAP as low as 80 mmHg, compared to contralateral RBF. However, with the other two methods where each kidney serves as its own control, a 15% RBF reduction was obtained at this RAP. This discrepancy (p less than 0.001) infers a contralateral renal vasoconstriction during ipsilateral renal hypotension and vasodilation. Arterial blood pressure increased during unilateral renal hypotension, suggesting that contralateral renal constriction was part of a general increase in total body vascular resistance. Following abrupt RAP reduction RBF was immediately readjusted (2-3 s) and maintained for up to 40 min. No significant change in intrarenal blood flow distribution was observed with I-Ap. Superficial and deep cortical single nephron glomerular filtration rates were equally reduced at lowered RAP as determined by the ferrocyanide technique. However, a dissociation between the autoregulation of RBF and glomerular filtration rate (GFR) in the direction of less well maintained GFR was observed. Renal arterial acetylcholine infusion increased RBF by about 40% and effectively abolished RBF autoregulation.

Renal uptake of 86Rb, lasting for 30s after intravenous bolus injection, and uptake of 15 micrometer radioactive microspheres (Ms) simultaneously injected in the left ventricle were measured in rats. Calculated from renal blood flow (RBF) determined by Ms and 86Rb clearance, the renal extraction ratio of 86Rb (ERb) was 0.81 +/- 0.07 (SD). With increasing RBF, ERb decreased significantly. Total body 86Rb extraction ratio nearly equalled ERb as determined 30s after injection. In another group of rats 86Rb was injected into an extracorporal circuit from the carotid artery perfusing the left kidney only. Renal recovery of 86Rb averaged 0.76 +/- 0.13 15-20s after injection. As in the first group, ERb was inversely related to RBF. At increased RBF, calculated local cortical flow is seriously underestimated unless ERb as well as ERb flow dependency are taken into account. However, the relative local flow rates calculated for cortical zones are not appreciably affected by ERb and its flow dependency.

Paired hydronephrotic (HN) and hypertrophic (HT) rat kidneys were studied after 6 days with complete unilateral ureteral obstruction without exposing the kidneys. Total HN renal blood flow (RBF), estimated by total microsphere (MS) uptake and from local 125I-antipyrine (Ap) uptake, averaged about 3/4 of control. HN kidney GFR was reduced to about 1/2 of control level as estimated from inulin clearance of HT kidney times the HN to HT ratio for mean single nephron filtration rate, determined by 14C-ferrocyanide. Whereas blood flow (Ap) was proportionately reduced in outer and inner cortex (OC and IC), fractional flow to the outer medulla (OM) was doubled as compared to controls (p less than 0.01). Filtration was well preserved in deep as compared to superficial glomeruli with a smaller deep nonfiltering fraction (p less than 0.02). Thus the results oppose the current concept that HN is characterized by disproportionate circulatory damage to IC and OM with little or no filtration in deep nephrons. In HT kidneys average RBF (MS) and GFR rose by about 1/2. Whereas total blood flow (Ap) rose proportionately in OC and IC, it remained at control level in OM, indicating dissociation between the total RBF and GFR and the effective blood flow to the OM zone.