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We describe a standardized clearance method over 5 h (one hour equilibration followed by eight consecutive 30 min clearance periods [period 2-9]) for the estimation of GFR (iothalamate I125) and ERPF (hippuran I131) during water diuresis in ambulatory and exercising patients. Four groups were examined. In group I (normal controls, n = 15) there were no significant changes in GFR, ERPF and FF (P0.10) during repeated clearance periods (mean of period 2-5 versus period 6-9). The reproducibility of the method was studied at a mean interval of 3.7 weeks in a group of patients with stable reduction of GFR (group II, n = 7). The values for GFR, ERPF, FF and RVR did not change significantly in this group, and correlated significantly between repeated studies (r = 0.81 to r = 0.99). In group III (untreated hypertensive patients with reduced GFR, n = 13) there was a time dependent 7.2% decrease in GFR (P0.05), significantly different from group I (P0.02), a 10.0% decrease in ERPF (P0.01) and no significant change in FF (P = 0.08) when the mean of period 2-5 was compared with the mean of period 6-9. In healthy controls (group IV, n = 8) light sustained bicycle exercise (25 W) induced a 7.1% decline in GFR (P0.01), 17.4% decline in ERPF (P0.001) and a 13.6% increase in FF (P0.001). We conclude that ambulatory measurements of GFR and RPF can be carried out over a period of 5 h with satisfactory precision and repeatability. Ambulatory hypertensive patients with moderately reduced GFR showed the same degree of time dependent downward drift of GFR and ERPF without exercise as was seen in healthy individuals during light exercise. Accordingly, in these groups single clearance periods imply a risk for under or overestimation of renal function, and time controls are necessary during clearance studies.

Autoregulation of total and zonal glomerular filtration rate (GFR) in outer, middle and inner cortex was estimated in spontaneously hypertensive rats (SHR), from the tubular uptake of 125I-labeled aprotinin (125I-Ap), injected at control renal arterial pressure (RAP), and 131I-Ap, injected at reduced RAP in left kidney. Normotensive Wistar-Kyoto (WKY) rats were used as controls. Renal blood flow (RBF) autoregulation was reset to higher pressure levels in SHR. When RAP was lowered close to the lower pressure limit of RBF autoregulation, total GFR was reduced to 89.5 +/- 3.1 and 88.1 +/- 3.3% of control in 10- and 40-wk WKY and to 87.7 +/- 2.3 and 88.0 +/- 2.2% in 10- and 40-wk SHR. In WKY, the fall of GFR in the three cortical layers was not different during RAP reduction. In 10- and 40-wk-old SHR, however, GFR fell significantly less in inner than in middle and outer cortex (P < 0.05). We conclude that autoregulation of GFR is most efficient in the inner cortex of SHR. In all animals, GFR was less well autoregulated than RBF.

The effect of acute and chronic indomethacin treatment on renal blood flow (RBF) autoregulation was studied in 10- and 40-wk-old spontaneously hypertensive rats (SHR). RBF autoregulation was substantially reduced in 40-wk-old SHR both during acute and chronic indomethacin treatment, whereas no effect was seen in the young SHR. The pressure range of autoregulation was 169 +/- 9 to 130 +/- 5 mmHg in the untreated 40-wk-old SHR, and 154 +/- 14 to 146 +/- 6 mmHg in indomethacin-treated 40-wk-old SHR (P less than 0.001). Indomethacin treatment had no effect on control RBF, mean arterial pressure, or renal vascular resistance in the 40-wk-old SHR. After removal of the renal nerves, RBF autoregulation during indomethacin treatment was restored in 40-wk-old SHR. The pressure range of RBF autoregulation was 158 +/- 7 to 142 +/- 7 mmHg in sham-operated animals, significantly different from the denervated 40-wk-old SHR, where RBF was autoregulated from 150 +/- 5 to 118 +/- 6 mmHg (P less than 0.01) during indomethacin treatment. The afferent arteriolar diameter (DAA) was studied by the microsphere method in 10-wk-old SHR and in untreated and indomethacin-treated 40-wk-old SHR. DAA was significantly greater in 40-wk-old compared with 10-wk-old SHR (22.1 +/- 0.4 vs. 17.9 +/- 0.5 microns) (P less than 0.01), whereas indomethacin treatment in 40-wk-old SHR did not influence the DAA significantly (21.5 +/- 0.3 microns, P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Interlobular arteries and afferent arterioles are involved in autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). The question of whether the contractile mesangial cells are also involved in autoregulation was investigated in Wistar rats. Autoregulation of RBF was examined before and 1 h after infusion of antithymocyte (anti-Thy 1-1) antibodies, and both RBF and GFR autoregulation were examined 30 h after the infusion of antibodies. Mesangial cell destruction was present 30 h after the infusion of antibodies. The angiotensin II-induced contraction of isolated glomeruli (70% of control volume, P less than 0.001) was abolished after the glomeruli had been exposed to anti-Thy 1-1 in vitro. RBF, as well as the lower limit of RBF autoregulation, were not different from control 30 h after the infusion (82 +/- 5 vs. 79 +/- 4 mmHg, P greater than 0.10). Autoregulation of GFR was maintained in the control group but was restricted in the experimental group (autoregulatory index: 0.71 +/- 0.42 for left kidney, 0.02 +/- 0.35 for control; P less than 0.05). The afferent arteriolar diameter was unchanged 30 h after the infusion of antibodies (17.8 +/- 0.8 vs. 17.6 +/- 0.4 microns, P greater than 0.10). One hour after infusion of the antibodies, RBF autoregulation was normal. It is concluded that mesangial cells do not seem to be involved in RBF autoregulation, but may in part influence autoregulation of GFR during pressure reduction.

In earlier studies, we have shown that induction of passive Heymann nephritis (PHN) by intrarenal infusion of anti-Fx1A antibodies provokes an immediate fall in renal blood flow (RBF) and glomerular filtration rate (GFR). This was probably mediated via the complement system, as infusion of the F(ab')2 fraction of anti-Fx1A did not reduce RBF and GFR. In the present study, the effects of alpha-adrenergic blockade upon the acute hemodynamic changes during induction of PHN and of C5a infusion were studied. Group 1 was infused with anti-Fx1A antibodies during blockade of the sympathetic nervous system with the alpha-blocker phentolamine; control animals were treated similarly, but infused with normal rat IgG. Group 2 was infused with the anaphylatoxin C5a, normally produced during complement activation, and compared with control animals infused with saline. In group 1, RBF did not differ from control animals after the infusion of anti-Fx1A antibodies (6.6 +/- 0.5 compared to 7.3 +/- 1.0 ml/min/g in the controls). GFR in the left, antibody-infused kidney fell compared to controls, and was 0.25 +/- 0.08 ml/min/g at the end of the experiment compared to 0.60 +/- 0.13 ml/min/g (p less than 0.05 with Student's t test, p = 0.07 with two-way analysis of variance (ANOVA). GFR in the right kidney remained unchanged compared to controls. In group 2, C5a induced a significant fall in RBF (from 7.9 +/- 0.9 to 3.1 +/- 0.4 ml/min/g kidney weight), significantly different from control animals where it fell from 8.1 +/- 0.5 to 6.8 +/- 0.7 ml/min/g (p less than 0.0001 with two-way ANOVA, p less than 0.001 with t test).(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular cell damage is an important mediator of interstitial fibrosis in chronic renal diseases. Glomerular and tubular damage in genetic hypertension was therefore studied. Tubular and glomerular damage was investigated in 10-, 40-, and 70-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared with glomerular capillary pressure (PGC) and glomerulosclerosis in superficial (OC) and juxtamedullary (JMC). Tubular vimentin was used as criterion of tubular damage. Variation in tubular diameter was measured during change in perfusion pressure, and ureter ligation was used to demonstrate the relationship between tubular pressure and appearance of vimentin-positive cells. Tubular and glomerular damage was most pronounced in JMC and greater in SHR than in WKY. It was absent in 10-wk-old WKY and significantly higher in JMC of SHR compared with WKY at 70 wk of age. Numbers of vimentin-positive segments were 18 ± 9 vs. 38 ± 7% in JMC of 70-wk-old WKY and SHR ( P < 0.02), and glomerulosclerosis was seen in 8 ± 3 vs. 19 ± 5% of glomeruli in JMC of 70-wk-old WKY and SHR, respectively ( P < 0.01). PGCwas 45 ± 3 mmHg in JMC of WKY and 57 ± 3 mmHg in JMC of 70-wk-old SHR ( P < 0.001). Tubular diameter variation was greatest in SHR ( P < 0.05) during pressure variation. Proteinuria was present only in 40- and 70-wk-old SHR and did not correlate with tissue damage. Tubular and glomerular damage in both strains develops in parallel and may be caused by a common mechanism, which may be glomerular capillary and tubular wall stretch during acute blood pressure variation which is greatest in JMC in SHR.

Increased physical activity is followed by a stimulation of the sympathetic nervous system and this effect is probably more pronounced in patients with chronic renal failure and hypertension than in healthy controls. The role of sustained exercise in hypertensive patients with chronic renal failure, with and without antihypertensive therapy, is unclear, as is hormonal regulation of the renal hemodynamics. We hypothesized that prolonged low-intensity bicycle exercise would have a greater effect in patients with chronic renal failure than in controls, and that antihypertensive treatment would ameliorate these effects.Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial blood pressure (MAP), norepinephrine (NE) and atrial natriuretic peptide (ANP) were measured in the upright position before and during low-intensity exercise for 2 h in healthy controls (n = 8) and in hypertensive patients with moderately reduced renal function who were not taking antihypertensives (n = 7) or who were receiving treatment with captopril (n = 10), enalapril (n = 6) or verapamil (n = 9).GFR tended to decrease and ERPF decreased significantly in healthy individuals when exercise duration was prolonged from 1 to 2 h. An earlier decline in GFR and ERPF was seen in the renal failure patients compared with the controls. Filtration fraction (FF) increased during exercise in all groups except the group taking enalapril. MAP increased in the captopril group during exercise but was unchanged in the other groups. Treatment with captopril produced a more pronounced and earlier fall in exercise-induced GFR than in untreated controls, while verapamil treatment completely blunted the decline in GFR, with a concomitant increase in plasma ANP. No significant changes were seen in plasma NE levels, but urinary NE excretion increased in controls and captopril-treated patients during exercise.The results suggest that prolonged low-intensity exercise has a substantially greater effect on renal hemodynamics in hypertensive renal failure patients than in healthy controls, with negligible changes in plasma NE levels. Verapamil treatment seems to ameliorate the renal effects of exercise on GFR in these patients, and this may in part be mediated via a stimulatory effect on ANP.

Renal tissue damage is substantially more pronounced in the juxtamedullary than in the superficial cortex in hypertensive rats, and the pathogenesis of the morphological changes are only partly understood. Glomerular capillary pressure (PGC) is increased, and steady-state autoregulation is normal in the deep renal cortex. We tested the hypothesis that the transient period from one pressure level to another may induce greater variation in local perfusion before stable autoregulation is established. An acute increase in local perfusion was compared in the superficial and juxtamedullary cortex of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) after an abrupt increase in perfusion pressure. Total renal blood flow (RBF) was measured by a Transonic flow probe and local renal perfusion by laser Doppler flowmetry. Renal perfusion pressure was lowered to 50% of initial values and released abruptly. The maximal RBF increased from 6.3 ± 0.4 to a maximal value of 7.6 ± 0.3 ml/min ( P < 0.001) in SHR and from 7.3 ± 0.3 to 8.2 ± 0.6 ml/min ( P < 0.001) in WKY. These changes were not significantly different from each other. The change in superficial cortical perfusion was also not different between SHR and WKY. Pressure release increased juxtamedullary perfusion in SHR from 146 ± 8 to a maximal value of 228 ± 17 units ( P < 0.001) and in WKY from 160 ± 13 to 179 ± 11 units ( P < 0.001). The results were significantly different from each other ( P < 0.001). The time for maximal flow response was shorter in the deep cortex of SHR, and the time for normalization was longer than in WKY. These data indicate that the buffering of perfusion pressure variation is significantly attenuated in the juxtamedullary cortex, and significantly more so in SHR than in WKY, assuming a covariation of RBF and PGC, and this finding may explain the extensive morphological damage in the juxtamedullary cortex of SHR.

The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys.Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions.Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p0.10). Plasma NE correlated positively with MAP (p0.001) and negatively with GFR (p0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p0.05).Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.

Angiotensin-converting enzyme inhibitors are renoprotective in diabetes mellitus through their intrarenal hemodynamic effects. Alpha-1 blockade has variable pre- and postglomerular vasodilatory effects dependent upon the stimulation of the sympathetic nervous system. We tested the hypothesis that the two different classes of drugs have similar renal hemodynamic effects when the patients are examined in an upright position where the sympathetic nervous system is activated. Mean blood pressure (MAP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were examined in 28 hypertensive type-1 diabetic patients with variable degree of nephropathy treated for a mean period of 7.6 ± 0.4 months with captopril (n = 13) or doxazosin (n = 15). Average treatment doses were 112 ± 7 mg/day in the captopril group and 8 ± 1 mg/day in the doxazosin group. Sitting MAP decreased from 118 ± 3 to 106 ± 4 mm Hg after captopril (p < 0.05), and from 117 ± 4 to 110 ± 3 mm Hg after doxazosin (p = 0.07). GFR and ERPF were unchanged in both groups. The filtration fraction (FF) decreased from 0.27 ± 0.02 to 0.25 ± 0.02 after captopril (p < 0.05) and from 0.26 ± 0.01 to 0.25 ± 0.01 after doxazosin (p = 0.08). Calculation of 95% confidence intervals of the difference between the post-treatment values as well as the difference between pre- and post-treatment values of MAP, GFR, ERPF and FF of the two drugs indicates no difference in renal hemodynamic response between the drugs. In conclusion, captopril and doxazosin have similar renal hemodynamic responses when the patients are examined in a situation where the sympathetic nervous system is stimulated, and this suggests that doxazosin has a renoprotective effect beyond the blood pressure-lowering effect.

Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is well maintained in the spontaneously hypertensive rat (SHR). In old SHR, the RBF autoregulation is dependent upon prostaglandins as well as the sympathetic nervous system. The purpose of this study was to examine the role of nitric oxide (NO) in the autoregulation of RBF and GFR in aging SHR (70 weeks) as compared with young SHR (10 weeks) and age–matched Wistar–Kyoto (WKY) rats using NO synthase (NOS) inhibition that has a minimal effect on the RBF. The autoregulation of RBF was examined using an adjustable aortic clamp above the renal arteries and an ultrasound Doppler flow probe on the left renal artery. The lower pressure limit of RBF autoregulation was examined before and after infusion of the NOS inhibitor NG–monometyl–L–arginine (L–NMMA; 500 μg·kg–1·min–1). Separate groups were given a coinfusion of L–NMMA and L–arginine (5 mg·kg–1·min–1) or Ringer solution. The autoregulation of the GFR was studied in continuously infused animals using the 125I–iothalamate clearance. Measurements of the GFR were done at control blood pressure, at a renal arterial pressure 10 mmHg above the lower pressure limit of RBF autoregulation and at a renal arterial pressure of about 60–65 mmHg. In both SHR and WKY rats, infusion of L–NMMA increased the mean arterial blood pressure, and the RBF decreased in young SHR, while the RBF was unchanged in the WKY groups and aged SHR. The autoregulation of RBF was maintained in all animals. The GFR was unchanged in all groups after infusion of L–NMMA, and the autoregulation of GFR was well maintained in all groups except in the 70–week–old SHR. In these animals, the fractional compensation of GFR decreased from 0.95 to ∼ 0 after infusion of L–NMMA, indicating that autoregulation of the GFR was lost during NOS inhibition. Coinfusion of L–NMMA and L–arginine normalized the GFR autoregulation in this group. The results indicate that in hypertensive rats with renal hypertensive damage, the GFR autoregulation is strongly NO dependent, as doses of L–NMMA that do not interfere with the RBF have an effect on the GFR autoregulation. As the GFR was unchanged during L–NMMA infusion, these observations suggest that postglomerular contraction during NOS inhibition may be involved in the regulation of GFR in 70–week–old SHR.

The relationship between systemic blood pressure and glomerular capillary pressure (Pgc) in spontaneously hypertensive rats (SHR) during treatment with antihypertensive drugs is still unclear. The effects of an angiotensin-converting enzyme inhibitor (enalapril), two calcium channel antagonists (nifedipine and verapamil), and an α1-receptor blocker (doxazosin) on renal blood flow (RBF) autoregulation, Pgc, and renal segmental resistances were therefore studied in SHR. Recordings of RBF autoregulation were done before and 30 min after intravenous infusion of the different drugs, and Pgcwas thereafter measured with the stop-flow technique. When the mean arterial pressure (MAP) was reduced to ∼120 mmHg by infusions of doxazosin or enalapril, the lower pressure limit of RBF autoregulation was reduced significantly. Nifedipine or verapamil abolished RBF autoregulation. Doxazosin did not change Pgc (43.6 ± 1.4 vs. 46.7 ± 1.5 mmHg in controls, P > 0.5), enalapril lowered (41.3 ± 0.8 mmHg, P < 0.01), and the calcium channel antagonists increased Pgc[53.7 ± 1.4 mmHg (nifedipine) and 54.8 ± 1.2 mmHg (verapamil), P < 0.01]. When MAP was reduced to ∼85 mmHg by drugs, Pgc was reduced to 43.3 ± 1.7 mmHg after nifedipine ( P > 0.2 vs. control), whereas Pgc after enalapril was 38.5 ± 0.5 mmHg ( P < 0.05 vs. control). Enalapril reduced Pgc mainly by reducing efferent resistance. During treatment with calcium channel antagonists, Pgc became strictly dependent on MAP. Monotherapy with nifedipine may increase Pgc and by this mechanism accelerate glomerulosclerosis if a strict blood pressure control is not obtained.

Decrease in systemic blood pressure, duration of pressure decrease, and change in the activity of the renin or the sympathetic nervous system may represent mechanisms involved in resetting the renal blood flow (RBF) autoregulation found in hypertensive rats. Autoregulation of RBF, plasma renin concentration (PRC), and the time needed for resetting to take place were studied in the nonclipped kidney before and after removal of the clipped kidney of two- kidney, one-clip (2K1C) hypertensive rats and before and after mechanical reduction of the renal arterial pressure (RAP) for 10 min in the spontaneously hypertensive rat (SHR) and in the nonclipped kidney of 2K1C hypertensive rats with and without renal denervation. Mean arterial pressure (MAP) fell from 147 to 107 mmHg 30 min after removal of the clipped kidney, and the lower pressure limit of RBF autoregulation decreased from 113 to 90 mmHg ( P < 0.01); PRC fell. Mechanical reductions of RAP from 161 to 120 mmHg in the nonclipped kidney for 10 min did not change RBF, but at 120 mmHg, the lower pressure limit of RBF autoregulation was reduced from 115 mmHg before pressure reduction to 96 mmHg afterwards ( P < 0.02). In SHR, similar pressure reduction for 10 min decreased the lower pressure limit of RBF autoregulation from 106 to 86 mmHg ( P < 0.01). PRC was unchanged in both models, and denervation did not change RBF autoregulation. When RAP was reduced below the lower pressure limit of RBF autoregulation, RBF decreased ∼20%; the lower pressure limit of RBF autoregulation remained unchanged. In normotensive Wistar-Kyoto rats, pressure reduction did not change the range of RBF autoregulation. These results indicate that acute normalization of the pressure range of RBF autoregulation in hypertensive rats is dependent on the degree of pressure reduction of RAP, whereas renal innervation and PRC do not play a major role. We propose that the mechanism of resetting is due to afterstretch of noncontractile elements of the vessel wall or is caused by pure myogenic mechanisms. An effect of intrarenal angiotensin cannot be excluded.

To gain insight into the mechanisms in the development of glomerulosclerosis in juxtamedullary cortex, the degree of glomerulosclerosis, glomerular tuft diameter, glomerular capillary pressure (Pgc), and local renal blood flow (RBF) autoregulation were measured in superficial and juxtamedullary cortex of 10- and 70-wk-old spontaneously hypertensive rat (SHR), using aged matched Wistar-Kyoto (WKY) rats as controls. Pgcwas measured after corticotomy by direct micropuncture of glomeruli in superficial and juxtamedullary cortex. Total RBF was measured by a transit-time flowmeter (Transonic) and local blood flow by use of laser-Doppler flowmetry. The degree of glomerulosclerosis measured by a semiquantitative histological technique was significantly increased in juxtamedullary compared with superficial cortex in all groups. The difference was most pronounced in the juxtamedullary cortex of 70-wk-old SHR. Pgcwas significantly increased in juxtamedullary cortex compared with superficial cortex in 70-wk SHR (57.1 ± 2.7 vs. 46.5 ± 0.5 mmHg, P < 0.01). The corresponding data set from 70-wk WKY was 45.5 ± 0.43 vs. 41.6 ± 1.5 ( P < 0.05). The Pgcin juxtamedullary cortex of 10-wk SHR was slightly higher than in superficial cortex (45.1 ± 2.3 vs. 50.1 ± 1.2 mmHg, P = 0.05), whereas there was no difference in 10-wk WKY. Glomerular diameter was larger in juxtamedullary cortex in old animals but not significantly different in 10-wk WKY rats and 10-wk SHR. Total RBF was reset to higher perfusion pressures in hypertensive rats. Juxtamedullary and superficial blood flow autoregulation were not significantly different from total RBF autoregulation in all groups. These results suggest that hypertrophy as well as increased Pgcmight contribute to the development of manifest glomerulosclerosis. Changes in local blood flow autoregulation do not seem to play a major role in the development of glomerulosclerosis.

We have earlier shown that there is an immediate fall in renal blood flow (RBF) and glomerular filtration rate (GFR) during induction of passive Heymann nephritis (PHN) by infusion of rabbit antibodies towards rat renal brush-border antigens (anti-Fx1A). To investigate the role of complement activation in this stage of the disease, we infused the F(ab')2 fraction of anti-Fx1A (aFFab) in one group of rats and the F(ab')2 fraction of normal rabbit IgG in another group (controls). aFFab produced no hemodynamic changes when compared to controls. Sixty minutes after infusion of aFFab, RBF was 5.7 +/- 0.4 ml/min/g kidney weight (control 7.3 +/- 1.0, NS), after anti-Fx1A RBF was 3.2 +/- 0.7, p less than 0.05 compared to control. GFR after infusion of aFFab was 1.0 +/- 0.1 ml/min/g (control 0.8 +/- 0.1, NS), after infusion of anti-Fx1A 0.2 +/- 0.1 (p less than 0.02 compared to control). The blood pressure was unaffected by aFFab infusion, while there was a temporary fall in blood pressure to a minimal value of 76 +/- 4 mm Hg 10-20 min after infusion of anti-Fx1A (p less than 0.01 compared to control). Immunofluorescence studies showed granular immune deposits in the subepithelial region of the glomerular basement membrane as shown after infusion of anti-Fx1A antibodies. In addition, fluorescence was seen in the brush-border of proximal tubuli. The results indicate that the immediate fall in RBF and GFR during induction of PHN in mediated via activation of the complement system.

When passive Heymann nephritis (PHN) is induced by infusion of antibodies (anti-Fx1A), an acute fall in renal blood flow (RBF) and glomerular filtration rate (GFR) has been reported. Activation of the complement cascade by the local antigen-antibody reaction might be involved in this reaction. We therefore studied RBF and GFR during acute infusion of anti-Fx1A and after 3 days when heterologous antibodies are no longer present in the circulation. Two groups of rats were infused with 2 mg anti-Fx1A antibodies into the left renal artery; RBF was measured by the microsphere method and GFR by 125I-Na-iothalamate clearance. In the first group, the measurements were made 40 min after the infusion, and in the second group after 3 days. A third group was studied 3 days after infusion of 1 mg anti-Fx1A. Animals infused with normal IgG were used as controls. Forty minutes after infusion of 2 mg anti-Fx1A, GFR in the left kidney was reduced from 1.16 +/- 0.07 to 0.41 +/- 0.16 ml/min/g in the controls (p less than 0.05). Three days after the infusion, GFR was 1.04 +/- 0.07, not significantly different from control. RBF was reduced to 3.97 +/- 1.11 ml/min/g after 40 min, compared to 7.53 +/- 0.73 in controls (p less than 0.05), and was normalized after 3 days. The effect of 1 and 2 mg anti-Fx1A antibodies was not significantly different after 3 days. Anti-Fx1A antibodies were detected in serum in the acute stage, but not after 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

The afferent arteriolar diameter (dAA) was investigated during development of hypertensive renal disease in normal and uninephrectomized control rats, in chronic DOCA-salt (DOCA), post-DOCA (p-DOCA), and chronic two-kidney one-clip (2K-1C) hypertensive rats, and in post-two-kidney one-clip (p-2K-1C) normotensive rats. dAA was measured by the microsphere method. Nephron loss was present in the kidneys exposed to elevate blood pressure. The dAA was reduced from 19.9 to 17.2 micron in the DOCA group (P less than 0.001) and from 19.1 to 16.3 micron in the nonclipped kidneys in the 2K-1C group (P less than 0.001). The dAA increased from 19.9 to 20.7 micron in the p-DOCA group. Afferent arteriolar dilatation from 19.1 to 21.0 micron (P less than 0.001) was present about 50 days after clipping in the 2K-1C group; in the clipped kidneys the dAA returned to normal (18.9 micron) after declipping. No relation between the dAA and plasma renin concentration was observed. In all models dAA was the same in three cortical layers of equal thickness. Accordingly, chronic renal DOCA-salt hypertension constricts the afferent arteriole with angiotensin-independent mechanisms. Autoregulatory dilatation of the afferent arteriole seems to be maintained for at least 50 days. When the hypertension is moderate, dAA in damaged kidneys may be dilated.

Acute passive Heymann glomerulonephritis in rats induced heavy proteinuria and highly increased urinary activity of N-acetyl-β-D-glucosaminidase, acid β-galactosidase and acid phosphatase. The cortical activity of these acid hydrolases was increased essentially in the large lysosomes as demonstrated by subfractionation of the lysosome-rich mitochondrial-lysosomal fraction, by rate zonal centrifugation. Banding density of small lysosomes shifted or reduced to slightly lower value (1.225 g/ml), which is between the banding densities of small ‘light’ (1.20 g/ml) and small ‘dense’ lysosomes (1.235 g/ml) in normal rat kidney cortex. Labelled protein reabsorbed in the proximal tubule is recovered in these populations of small lysosomes as well as in the large lysosomes or ‘protein droplets’. Glomerulonephritis also induced a new population of small ‘light’ lysosomes (density 1.185–1.195 g/ml) enriched in cathepsin D. The previously demonstrated morphological, biochemical, and physiological heterogeneity of renal lysosomes was confirmed and emphasized in the kidney cortex of glomerulonephritic rats. The main changes in the lysosomal populations appear to reflect the increased protein reabsorption as confirmed by the proteinuria.

Renal blood flow (RBF) autoregulation was examined in untreated 10- and 40-wk-old spontaneously hypertensive rats (SHR) [mean arterial pressure (MAP) 125 +/- 4 and 167 +/- 7 mmHg] and in captopril-treated (7 days) 10- and 40-wk-old SHR (88 +/- 7 and 112 +/- 5 mmHg). Age-matched Wistar-Kyoto rats (WKY) were used as controls (MAP 91 +/- 3 and 104 +/- 2 mmHg). The study was carried out in rats with and without acute uninephrectomy. In 10-wk-old acutely uninephrectomized animals, the lower pressure limit of autoregulation was 78 +/- 4 mmHg in WKY, 102 +/- 5 mmHg in SHR (P less than 0.02), and 78 +/- 7 mmHg in captopril-treated SHR (P greater than 0.10). The renal vascular resistance (RVR) was significantly elevated at the lower pressure limit of RBF autoregulation in untreated SHR (P less than 0.02) but became normal after treatment (P greater than 0.10). Neither uninephrectomy nor variation of RBF between different batches seemed to influence the lower pressure limit of RBF autoregulation. In 40-wk-old acutely nephrectomized animals, the lower pressure limit of RBF autoregulation in WKY was 85 +/- 4 mmHg, 128 +/- 3 mmHg in SHR (P less than 0.001), and 101 +/- 5 mmHg in captopril-treated SHR (P less than 0.01). RVR at the lower pressure limit was increased in untreated SHR (P less than 0.01), but fell to normal values during captopril treatment. Neither the uninephrectomy nor variation of RBF between different batches of rats seemed to influence the lower pressure limit of RBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of fasting on lysosomes in kidney cortex of glomerulonephritic rats. The effect of food restriction (FR) on the kidney cortex lysosomes prepared by rate and isopycnic zonal centrifugation was studied in rats with passive Heymann glomerulonephritis (PHN). FR reduced ttie renal mass by 41%, but the capacity for handling of labelled endocytosed proteins by the lysosomes was not different from fed PHN rats. While PHN with heavy proteinuria increased the recovery of lysosomal enzymes in the large lysosomes located in the proximal tubule, no changes were observed in FR-PHN rats in spite of significant proteinuria. The density of the small lysosomes was significantly shifted/reduced (from 1,200 and 1,235 g/ml to 1,185 and 1,225 g/ml, respectively) in both fed and FR-PHN rats, suggesting that the handling of extra loads of protein may enhance the absorbtive function of small lysosomes found in the lower part of the nephron. FR reduced the mechanical fragility of lysosomes in the kidney cortex of PHN-rats. The highly increased urinary excretion of lysosomal enzymes in fed PHN rats was not observed in FR-PHN rats. As a conclusion, FR reduces both the fragility of lysosomes and the proportion of digestive enzymes in fragile lysosomes. These lysosomal enzymes may be of pathogenic importance in PHN causing cell damage when liberated from disrupted lysosomes.

The dye dilution curves from twelve human kidneys were compared with systemic curves from the same individuals recorded at the same time. The recirculation distance was the same for both types of recording.The renal curves were constantly influenced by recirculating dye. The initial deviation from the linear semilogarithmic extrapolation of the down slope of the renal curves occurred before the minimal re-circulation time and could be caused by inadequate mixing of dye in the renal artery, leakage of dye into the extravascular space or by the medullary circulation.

Autoregulation of renal blood flow (RBF) was investigated in subacute (2 mo) and chronic (18 mo) passive Heymann nephritis (PH-2, PH-18) and age-matched controls (C-2, C-18). RBF was significantly lower in PH-18 than in C-18 (3.7 +/- 0.4 vs. 4.7 +/- 0.5 ml.min-1.kidney-1; P less than 0.05), whereas the mean blood pressure (MAP) was similar. The creatinine clearance was significantly lower in PH-18 than in C-18 (1.89 +/- 0.5 vs. 3.15 +/- 0.77 ml.min-1.kg body wt-1; P less than 0.002). Kidney weight was significantly higher in PH-18 than in C-18 (P less than 0.002). In PH-2 and C-2, RBF, MAP, creatinine clearance, and kidney weight were not different (P greater than 0.10). In PH-18 the maximal reduction of the renal vascular resistance (RVR) during RBF autoregulation was 4 +/- 2%, compared with 24 +/- 4% in C-18 (P less than 0.002); the lower pressure limit of RBF autoregulation was 131 +/- 9 vs. 85 +/- 4 mmHg (P less than 0.002). In PH-2 the maximal reduction of RVR during RBF autoregulation was 18 +/- 3%; in C-2 it was 25 +/- 2% (P greater than 0.10); the lower pressure limit of RBF autoregulation was 101 +/- 4 vs. 84 +/- 6 mmHg (P less than 0.02). It is concluded that RBF autoregulation is nearly lost in the late stage of glomerulonephritis, possibly as a consequence of the nephron loss.

Microscopical examination of the urinary sediment has been performed after membrane filtration and after routine centrifugation, and the results were compared. Various quantities of urine were filtered through a membrane with pore size of 3 micrometer, stained with Shorr stain and made translucent with xylol. All granular and cellular casts were counted on a trimmed membrane, 15 X 20 mm. The routine centrifugation was carried out on 10 ml urine at 1500 rpm for 3 min. Among 11 patients with glomerulonephrits and recurrent hematuria, casts were found in 9 after filtration but in only 2 after routine centrifugation. Casts were detected by the filter method in the urine after angiography of the kidneys in 8 of 12 patients, after centrifugation in only one of them. No casts were found in 6 patients with hematuria due to urological disorders and in 21 healthy persons. The diagnostic sensitivity of microscopical examination of urine was greatly increased by the filter method. This may be due to larger amount of urine examined by the filter method, but an additional cause may be that routine centrifugation destroys red cell casts.

In glomerulonephritic and normal kidneys hypertension has been shown to increase the urinary protein excretion and the thickness of the glomerular basement membrane and to reduce the glomerular filtration rate. We have studied the effect of desoxycorticosterone acetate (DOCA)-salt hypertension on the glomerular anatomy and function in normal control rats and rats with passive Heymann nephritis. Standard methods for measurements of glomerular filtration rate and urinary protein excretion were used and the results were correlated to morphometrical measurements in randomly selected glomeruli in all groups. In control rats, DOCA-salt hypertension increased the kidney weight (P less than 0.001), the glomerular volume (P less than 0.05), and the surface of peripheral glomerular basement membrane (P less than 0.01). The thickness of peripheral glomerular basement membrane and the length of glomerulary capillaries were not affected. In glomerulonephritic rats, DOCA-salt hypertension did not change the kidney weight and glomerular capillary diameter. The thickness of the peripheral basement membrane increased (P less than 0.05), while the length of glomerular capillaries and the surface of peripheral basement membrane were reduced (P less than 0.05). Glomerular filtration rate per unit peripheral basement membrane was not significantly different among the groups while protein excretion per unit peripheral basement membrane increased significantly both in the hypertensive and in the glomerulonephritic groups. The estimated hydraulic conductivity of the glomerular capillaries was reduced both in rats with DOCA-salt hypertension and glomerulonephritic rats with and without DOCA-salt hypertension. In conclusion, DOCA-salt hypertension seems to decrease hydraulic conductivity and increase protein excretion both in normal and in glomerulonephritic kidneys although the effect on glomerular morphology is different.

The pathophysiology, histology and immunohistology of acute and chronic heterologous immune complex glomerulonephritis were investigated in a long-term study in male Wistar rats. The glomerulonephritis showed 3 phases: an initial nephrotic syndrome, a latent phase with stable proteinuria (40 mg/24 h), and a terminal phase with increasing proteinuria and blood pressure, and declining serum protein concentration and creatinine clearance. Antiserum doses of 1.0, 1.5 and 2.0 ml induced maximal proteinuria (112, 257 and 272 mg/24 h respectively) after 14 days whereas normal rabbit serum and 0.5 ml antiserum gave no proteinuria. After 100 days, the rats injected with 1.0 ml of antiserum did not show physiological signs of renal disease; in the rats injected with 1.5 ml of antiserum the disease run a chronic course. Equal amounts of rabbit IgG, rat IgG and rat C3 were found in 10 glomeruli from rats 100 days after injection of 0.5, 1.0 and 2.0 ml (p greater than 0.10). Intramembranous deposits and spike formation were observed in all groups. All changes increased with greater antiserum doses. Chronically diseased animals observed from 500 to 750 days showed deposits of rabbit IgG in the basement membrane, and in most animals small amounts of rat IgG and rat C3 were also observed. This is compatible with a sustained stimulus for antibody formation throughout the course of this type of glomerulonephritis.

Microspheres with diameters of from 10 to 30 mum were injected into the renal arteries of three anesthetized dogs. The six kidneys were studied by light microscopy. The diameters of the spheres trapped in the afferent arterioles and of all spheres recovered in the kidneys were recorded. On the basis of the distribution of diameters in these two populations of spheres, the average diameter of the afferent arteriole and the distribution of the afferent arteriolar diameters were estimated. The average diameter of the afferent arterioles was 16.3 mum (S.D. 2.2 mum), without any difference between three cortical layers of equal thickness. The mean diameter of spheres trapped in the interlobular arteries was 25.7 mum (S.D. 2.6). It is suggested that the pressure drop along some interlobular arteries may be of physiological importance, affecting the autoregulation of blood flow in the renal cortex.

Heavy and light microsomal fractions were subfractioned using high performance zonal rotors, and assayed for approtenin sensitive kallikrein- like amidolytic activity (pH 8.2). The activity profiles for the various substrates assayed show rather complex distribution pattern demonstrating kallikrein-like amidolytic activity in plasma membranes, basolateral membranes, rough endoplasmic reticulum and membranes derived from the Golgi complex.

Subcutaneous oedema is a common finding in heart failure. However, some patients have reduced cardiac pump function without oedema. The aim of this study was to investigate whether local mechanisms in subcutaneous tissue contribute to oedema prevention. A reduction in interstitial colloid osmotic pressure (pii) and a rise in interstitial fluid hydrostatic pressure (Pi) will both counteract a rise in capillary filtration caused by heart failure. Cardiac catheterization was done in 22 angina pectoris patients without visible oedema. Two days later pii was measured with a wick method and Pi was measured with a wick-in-needle method. Both parameters were measured in subcutaneous tissue on thorax at heart level and on the ankle. Plasma volume was determined by 125I-albumin and extracellular volume measured with 35SO4. Parameters of cardiac pump function ranged from normal to clearly pathological values. Mean pii was 13.0 mmHg on thorax and 8.3 mmHg on the ankle. Pi averaged -2.1 mmHg on thorax and -1.5 mmHg on the ankle. Statistically significant (P less than 0.05) correlations were found between pii on thorax and left ventricular end diastolic pressure (rs -0.40) and pii on thorax and cardiac index (rs 0.42). Pi was positively correlated to right atrial pressure (rs 0.50). Body fluid volumes were normal or moderately reduced. The study shows that a reduction in cardiac pump function is associated with a reduction in pii and a rise in Pi. These changes may help to prevent oedema formation in the early stages of heart failure.

Retroperitoneeal fibrosis (R.P.F.) and a positive direct Coombs test developed in a patient who had received 1.4 kg. of alpha-methyldopa over a period of 5 years. Immunofluorescence microscopy demonstrated deposits of IgG, IgM, and IgA on the collagen fibres of the R.P.F. Biopsy speciments of the temporal artery, the right kidney, and the R.P.F. did not show signs of general arterial disease on light, immunofluorescence, and electron microscopy. Drugs which provoke autoimmunisation and interfere with nervous transmission are known to induce deposition of collagen or R.P.F. This suggests that R.P.F. in this patient was probably caused by alpha-methydopa.

The importance of the peritubular physical factors as mediators of the natriuretic response to saline volume expansion was examined in twenty normotensive, hydropenic indivduals. Intrarenal venous pressure (IRVP), used as a measure of peritubular capillary hydrostatic pressure, and efferent arteriolar colloid osmotic pressure, calculated from arterial colloid osmotic pressure and the filtration fraction, were measured before and during sustained volume expansion with 0.9% NaCl, increasing the body weight by 3% and plasma volume about 20%. During expansion there was a significant increase in urine flow from 1.1 +/0 0.1 to 3.1 +/- 0.4 ml/min and sodium excretion from 161 +/- 12 to 551 +/- 61 microEq/min. Efferent colloid osmotic pressure fell from 31.9 +/- 0.6 to 23.6 +/- 0.5 mmHg (P less than 0.001) while IRVP changed from 24.8 +/- 0.8 to 25.1 +/- 0.9 mmHg (P greater than 0.10). In eight individuals IRVP increased during saline loading but later fell during sustained expansion. Glomerular filtration rate and renal blood flow did not change significantly. It is concluded that increase in peritubular capillary hydrostatic pressure is not necessary either to induce or to maintain the natriuresis of a moderate saline volume expansion. Although the fall in postglomerular vascular colloid osmotic pressure is a possible mediator of the natriuretic response, the change in peritubular transcapillary net driving force produced by a modest saline volume expansion is probably small.

The participation of the afferent arterioles (AA) in RBF autoregulation was studied in two groups of rats (groups A and B) by measurement of the afferent arteriolar diameters (dAA) by the microsphere method at control pressure (groups A and B), at the lower pressure limit of RBF autoregulation (group A) and at a perfusion pressure half-way between these pressures (intermediate pressure) (group B). The RBF was autoregulated from 109 +/- 7 (control pressure) to 80 +/- 7 mmHg (lower pressure limit) in group A, and from 101 +/- 4 (control pressure) to 77 +/- 3 mmHg in group B. In group A, dAA was significantly lower (17.2 +/- 0.3 micron) at control pressure than at the lower pressure limit of RBF autoregulation (20.3 +/- 0.03 micron) (P less than 0.005). In group B, dAA was 17.3 +/- 0.3 micron at control pressure and 17.1 +/- 0.4 micron at the intermediate pressure (89 +/- 3 mmHg) (P greater than 0.10). The results indicate that dilation of the afferent arterioles occurs only in the lower part of the autoregulatory pressure range. Possibly, RBF autoregulation at minor pressure reductions is achieved by dilation of the interlobular artery. Participation of the glomerular hilar branches of the afferent arterioles in RBF autoregulation cannot be excluded.

To examine the validity of intrarenal venous pressure (IRVP) as a measure of peritubular capillary pressure when obtained with a method applicable in man, IRVP was measured with a 0.9 mm o.d. catheter introduced retrograde into interlobar veins of anesthetized dogs and was compared with a modified needle pressure (cortical catheter pressure = RCCP) measured simultaneously in the same kidneys. In twelve dogs with a mean experimental kidney control sodium excretion of 91 +/- 15 (SEM) micronmol/min IRVP averaged 16.0 +/- 1.1 mmHg and was significantly lower than the average RCCP of 22.6 +/- 1.1 mmHg (P less than 0.001). These pressures compare well with the reported micropuncture pressures in the peritubular capillaries and proximal tubules, respectively, at comparable levels of sodium excretion. IRVP fell significantly during reduction of renal perfusion pressure within the range of autoregulation of renal blood flow and increased during elevation of renal pelvic pressure (PP). At at PP of 60 mmHg, when urine flow had stopped, the PP-IRVP gradient was 22.7 +/- 3.1 and increased to 36.7 +/- 3.8 (P less than 0.001) at a PP of 80. Acute renal vein constriction always increased IRVP before renal vein pressure reached the preceeding control level of IRVP. Increased urine flow during saline volume expansion and furosemid infusion was associated with increased IRVP. The results when compared with micropuncture data indicate that IRVP is a satisfactory expression of peritubular capillary pressure in the experimental conditions included in the study.

The acute renal hemodynamic changes during induction of passive Heymann nephritis (PHN) may be of importance for the understanding of the pathogenesis of this model. We studied the renal blood flow (RBF) and glomerular filtration rate (GFR) during and after infusion of anti-FxlA into the left renal artery of rats for 10 min. 3 control groups were given 0.9% NaCl, 1 and 2 mg of normal rabbit IgG, respectively. The experimental groups were given 1 and 2 mg IgG fraction of anti-FxlA. Compared to controls, both RBF and GFR were substantially reduced during the first 20-30 min after infusion and remained unaltered for the rest of the observation period. After 20-30 min, RBF in the 1-mg group was 4.8 +/- 0.77 ml/min/g kidney weight versus control, 6.4 +/- 1.23 (NS), and in the 2-mg group, 3.5 +/- 0.65 ml/min/g versus control, 6.4 +/- 1.07 (p less than 0.05). Similarly, in the 1-mg group, GFR was 0.40 +/- 0.08 ml/min/g versus control, 0.76 +/- 0.11 (p less than 0.05), and in the 2-mg group, 0.14 +/- 0.05 versus control, 0.77 +/- 0.12 (p less than 0.0001). The reductions were greater in the 2-mg than in the 1-mg infused experimental groups, but this difference did not reach statistical significance. Immunofluorescence showed typical granular fluorescence of rabbit IgG along the glomerular basement membrane, and electron microscopy showed subepithelial immune deposits. This indicates that in the initial phase of PHN, corresponding with the formation of immune complexes, a pronounced fall in RBF and GFR occurs.

Renal blood flow (RBF) autoregulation was examined in the clipped and nonclipped kidneys in two groups of two-kidney, one-clip (2K-1C) hypertensive rats 10 wk after clipping. The arterial pressure distal to the clip and the renin secretion rate (RSR) were also examined. The blood pressure (BP) was 149 +/- 4 and 162 +/- 6 mmHg in the two hypertensive groups vs. 114 +/- 3 mmHg in the controls (P less than 0.02). The RBF (in ml X min-1 X kidney-1) was 4.27 +/- 0.41 in the nonclipped and 2.18 +/- 0.23 in the clipped kidneys (P less than 0.001). The pressure distal to the clip was 104 +/- 7 mmHg. The renal vascular resistance (RVR) (in mmHg X ml-1 X min-1 X g-1) was 25.0 +/- 1.4 in the control kidneys vs. 58.4 +/- 4.5 in the nonclipped (P less than 0.001) and 39.9 +/- 6.6 in the clipped kidneys (P less than 0.01). The RBF autoregulation was well preserved in the nonclipped kidneys but reset to a higher lower pressure limit of autoregulation of 106 +/- 4 mmHg, which was significantly higher than in the normotensive controls (84 +/- 6 mmHg) (P less than 0.01). In the clipped kidneys there was complete loss of RBF autoregulation. RSR decreased with reduction of the perfusion pressure in the clipped kidneys. The increased RVR might have been due to a combination of structural and functional changes in both kidneys.

The tissue osmolality has been measured in three human kidneys. In the presence of considerable osmotic gradients between the subpapillar part of the pyramids and the renal columns, no significant difference between the osmolality of the renal columns and the cortex proper was observed. Similar findings were obtained in two ox kidneys. Thus the establishment of medullary hyperosmolality does not seem to be seriously affected by the presence of renal columns.

Isotope-labeled microspheres with an average diameter of 15 μ and 25 μ, and isotope-labeled macroalbumin (131MA) were injected into the aorta of 26 dogs before or after the animals were bled to hemorrhagic hypotension. The localization of the microspheres was studied by microscopical examination and the intrarenal distribution of the radioactivity was measured. No significant effect of the hemorrhagic hypotension upon the distribution of radioactivity or the number of microspheres in different cortical layers was observed in normal kidneys. In surgically manipulated kidneys the hypotension provoked a relative increase of the radioactivity in the middle and juxta-medullar parts of the renal cortex. In the early phase of hemorrhagic hypotension the fraction of spheres with a diameter greater than 20 μ recovered in the glomeruli increased from zero to 6.3% when compared with normotensive animals; this indicates a dilatation of the afferent arterioles in this phase of hemorrhagic hypotension.

In 32 patients with unilateral, parenchymatous renal disorders (16 with hypertension), filtration fraction of affected and normal kidneys, and the ratio between filtration fractions of affected and normal kidneys, were greatest in hypertensive patients. The excretion fraction of sodium and the osmotic clearance per unit glomerular filtrate were greater and the urinary concentration of inulin was least in affected kidneys without difference between normotensive and hypertensive patients. It is suggested that hypertension affects diseased and normal kidneys in the same way.