Pressure in the glomerular capillaries of the rat kidney and its relation to arterial blood pressure

Summary The pressure in the glomerular capillaries of the rat kidney was determined by micropuncture of individual nephrons. The proximal tubule was blocked by injection of viscous oil. The intratubular hydrostatic pressure increased until it reached a steady state, the intratubular stop-flow pressure. Since the glomerular capillary wall is an ultrafiltration membrane, impermeable to proteins, the sum of intratubular stop-flow pressure plus the plasma colloid osmotic pressure should equal the pressure in the glomerular capillaries. This pressure increased as the arterial pressure was raised from 60 to 90 mm Hg. Thereafter it remained constant at 88±4 mm Hg despite further elevation of the arterial pressure up to 160 mm Hg. Determination of the stop-flow pressure in Bowman's capsule and in the proximal tubules of denervated kidneys gave the same results as above.The hydrostatic pressure drop in the afferent arterioles was determined by subtracting the glomerular capillary pressure from the arterial pressure. This pressure drop was negligible at arterial pressures below 90 mm Hg and increased linearly as the arterial pressure was elevated from 90 to 160 mm Hg.Both the above findings are compatible with and confirm the principle of autoregulation of renal blood flow and glomerular filtration rate.Supported by NIH Grant Nr. AM 06806-03 and by Deutsche Forschungsgemeinschaft.From the Dept. of Pediatrics, University of Wisconsin, Madison, Wisconsin, U.S.A. Supported by the National Cystic Fibrosis Foundation.     

Dynamics of glomerular ultrafiltration in Amphiuma means

To study renal function inAmphiuma means, the hydrostatic pressures in vascular and tubular structures and the glomerular filtration rate were determined at different arterial blood pressures. In the arterial blood pressure range studied no evidence of autoregulation of the glomerular capillary pressure or of the hydrostatic pressure gradient over the capillary membrane was found. The glomerular filtration ceases at an arterial blood pressure below 12 cm H₂O. No significant difference between tubular free flow pressure and peritubular capillary pressure was noted. Furthermore, it was found that the glomerular capillary pressure could be estimated by measuring the intratubular stop-flow pressure and arterial colloid osmotic pressure at an arterial pressure above 15 cm H₂O. It was also found possible to measure the glomerular capillary pressure at the very end of the afferent arteriole. The protein concentrations in afferent and efferent arteriolar blood were determined and the colloid osmotic pressures were calculated according to a new formula derived forAmphiuma plasma. The dynamics of glomerular ultrafiltration was evaluated. A filtration equilibrium across the glomerular membrane was reached, since the efferent colloid osmotic pressure was not significantly different from the hydrostatic pressure gradient across the glomerular capillary membrane.     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.     

The anatomy and blood system of the kidney in the river lamprey, Lampetra fluviatilis

Summary The anatomy and blood system of the kidney in the river lamprey, Lampetra fluviatilis, was studied after injecting microfil into nephrons or the arterial system. Renal arteries arose at irregular intervals from the dorsal aorta and gave rise to a regular arrangement of afferent arterioles supplying the network of glomerular capillaries. Nephron units were arranged in two longitudinal series on each side of the glomerular capillaries, with the capsule of each nephron closely related to the capillary network. A short neck segment lead into the convoluted proximal segment, which accounted for over half the length of each nephron and was surrounded by a network of capillaries and sinusoids supplied by efferent glomerular arterioles. The end of each proximal segment formed the descending limb of a nephron loop, which lay parallel to the ascending distal limb and the end of each collecting duct. Peritubular blood flow in this region was generally opposite the flow of tubular fluid and blood eventually drained into large thin-walled sinuses connected to the post-cardinal vein.This work was supported by SRC research grant number GR/A 1820.7. We thank Miss V. Griffiths for technical assistance and Mr. P. Gaskins for the supply of lampreys     

Kinetics of the Glomerular Ultrafiltration in the Rat Kidney. A Theoretical Study

The glomerular filtration process was evaluated theoretically from micropuncture data obtained from Sprague-Dawley rats. The hydrostatic pressures in the glomerular capillaries and Bowman's space minus the oncotic pressure in systemic plasma gave the net driving force at the proximal end of the glomerular capillary. From the single nephron filtration fraction the mean net driving force over the glomerular membrane was calculated to be 20 mm Hg during normotension, decreasing to 12 mm Hg during a perfusion pressure of 80 mm Hg. The hydraulic permeability for one glomerulus was 0.7-0.8 nl/min. 100g b. wt. mmHg. The pressures at the distal end of the glomerular capillaries were 13 and 6 mm Hg under the above two conditions, indicating non-equilibrium of the filtration process at the end of the glomerular capillary. It was shown that the glomerular filtration rate is mainly influenced by the driving pressures. During hypotension an increased plasma flow dependency was evident. Brenner et al. found a filtration equilibrium and a plasma flow dependent glomerular filtration rate in a mutant Wistar rat strain. The discrepancy between their results and ours is due to the low glomerular plasma flow and hydrostatic pressures in the Wistar rats. It is concluded from our results that both pre- and postglomerular resistances may influence the glomerular filtration rate and glomerular plasma flow independently.     

Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate

The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE₂ release (veno-arterial concentration difference times renal plasma flow) from 1.7 ± 0.9 to 9.1 ±0.4 and 6-keto-PGFja release from 0.1 ±0.1 to 5.3 ± 2.1 pmol min^-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 ± 8%. Blockade of prostaglandin synthesis approximately doubled the vasocon-strictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8± 13.3 and 15.9± 5.4 pmol min^-1 for PGE₂, and 6-keto-PGFja, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25–30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.     

A multinephron model of renal blood flow autoregulation by tubuloglomerular feedback and myogenic response

Tubuloglomerular feedback implies that a primary increase in arterial pressure, renal blood flow, glomerular filtration and increased flow rate in the distal tubule increase preglomerular resistance and thereby counteract the primary rise in glomerular filtration rate and renal blood flow. Tubuloglomerular feedback has therefore been assumed to play a role in renal autoregulation, i.e., the constancy of renal blood flow and glomerular filtration at varying arterial pressure. In evaluating this hypothesis, the numerous tubular and vascular mechanisms involved have called for mathematical models. Based on a single nephron model we have previously concluded that tubuloglomerular feedback can account for only a small part of blood flow autoregulation. We now present a more realistic multinephron model, consisting of one interlobular artery with an arbitrary number of evenly spaced afferent arterioles. Feedback from the distal tubule was simulated by letting glomerular blood flow exert a positive feedback on preglomerular resistance, in each case requiring compatibility with experimental open-loop responses in the most superficial nephron. The coupling together of 10 nephrons per se impairs autoregulation of renal blood flow compared to that of a single nephron model, but this effect is more than outweighed by greater control resistance in deep arterioles. Some further improvement was obtained by letting the contractile response spread from each afferent arteriole to the nearest interlobular artery segment. Even better autoregulation was provided by spreading of full strength contraction also to the nearest upstream or downstream afferent arteriole, and spread to both caused a renal blood flow autoregulation approaching experimental observations. However, when the spread effect was reduced to 25% of that in each stimulated afferent arteriole, more compatible with recent experimental observations, the autoregulation was greatly impaired. Some additional mechanism seems necessary, and we found that combined myogenic response in interlobular artery and tubuloglomerular feedback regulation of afferent arterioles can mimic experimental pressure-flow curves.     

Segmental distribution of vascular resistances during ureteral occlusion: The vasoconstrictive effects of angiotensin and CaCl2 differ from those of catecholamines and renal nerve stimulation

Examinations of renal autoregulation and renin release suggest that α-adrenergic agonists, in contrast to other vasoconstrictors, preferentially constrict the preglomerular arteries. To examine this hypothesis, experiments were performed in anesthetized dogs during ureteral occlusion. At a ureteral pressure (UP) of 100 mmHg the afferent arterioles are dilated and mechanical constriction of the renal artery does not alter intrarenal vascular resistances. Whereas angiotensin and CaCl₂ infused into the renal artery reduced renal blood flow (RBF) by 25–30% without reducing UP, renal nerve stimulation reduced RBF and UP in proportion. During angiotensin and catecholamine infusion, measurements of UP and intrarenal venous pressure permitted calculations of preglomerular, efferent vascular and intrarenal venous resistances. Until RBF was reduced by 25%, angiotensin raised both preglomerular and efferent vascular resistances, whereas norepinephrine and the α-adrenergic agonists, phenylephrine and methoxamine raised preglomerular more than efferent vascular resistance. When RBF was reduced by more than 25%, all vasoconstrictors showed a similar pattern with large increments both in preglomerular and efferent vascular resistances. Conclusions: Humoral and nervous stimulation of α-adrenergic receptors reduce glomerular capillary pressure by preferentially constricting the preglomerular arteries and may affect renal autoregulation and renin release by reducing the transmural pressure of the afferent arterioles.     

Kinetics of the glomerular ultrafiltration in the rat kidney. A theoretical study.

The glomerular filtration process was evaluated theoretically from micropuncture data obtained from Sprague-Dawley rats. The hydrostatic pressures in the glomerular capillaries and Bowman's space minus the oncotic pressure in systemic plasma gave the net driving force at the proximal end of the glomerular capillary. From the single nephron filtration fraction the mean net driving force over the glomerular membrane was calculated to be 20 mm Hg during normotension, decreasing to 12 mm Hg during a perfusion pressure of 80 mm Hg. The hydraulic permeability for one glomerulus was 0.7-0.8 nl/min-100 g b.wt. mmHg. The pressures at the distal end of the glomerular capillaries were 13 and 6 mm Hg under the above two conditions, indicating non-equilibrium of the filtration process at the end of the glomerular capillary. It was shown that the glomerular filtration rate is mainly influenced by the driving pressures. During hypotension an increased plasma flow dependency was evident. Brenner et al. found a filtration equilibrium and a plasma flow dependent glomerular filtration rate in a mutant Wistar rat strain. The discrepancy between their results and ours is due to the low glomerular plasma flow and hydrostatic pressures in the Wistar rats. It is concluded from our results that both pre- and postglomerular resistances may influence the glomerular filtration rate and glomerular plasma flow independently.     

Aglomerular pathways in intrarenal microvasculature of aged rats

By means of silicone rubber injections, we confirmed the existence of several types of aglomerular arterial pathways within kidneys of aged rats. In superficial cortex some interlobular arteries divide to form aglomerular branches (Ludwig's arterioles) towards cortex corticis. In juxtamedullary cortex these pathways are relatively more numerous, they comprise: (a) Vasa Recta Vera, (b) glomeruli in which afferent and efferent arterioles form a continuous vessel and (c) glomeruli with two efferent vessels, one by-passing glomerular tuft. In addition, results obtained in the rat by the microsphere technique are in agreement with our morphological observations.     

Changes in the Filtration Fractions in the Superficial and Deep Venous Drainage Area of the Gat Kidney due to Fluid Loading

The effect of Ringer and mannitol loading on the filtration fractions of plasma entering the superficial and the deep part of the cortex was investigated by comparing the plasma concentrations of inulin and protein in the blood leaving the two venous drainage areas with the concentrations in arterial blood. The ratio between the deep and the superficial filtration fraction (FF_D/FFs) decreased by some 20 per cent mainly due to a decrease in FF_D. Inside the juxtamedullary glomeruli, which constitute a part of the glomeruli of the deep area, short-circuits between the afferent and the efferent arterioles have been described, which cause the medullary blood supply to partly by-pass the sites of ultrafiltration. The blood leaves the juxtamedullary glomeruli via relatively thick muscular efferent arterioles which regulate the medullary blood flow. The decrease in FF_D may result from a preferential augmentation of the flow through the medulla, viz. this indicates that the overall filtration fraction of the deep drainage area to a larger degree is governed by the presumably low filtration fraction of the juxtamedullary glomeruli.     

Renal microvasculature of the rainbow trout, Salmo gairdneri: scanning electron microscopy of corrosion casts of glomeruli

Scanning electron microscopy of corrosion casts of blood vessels permits detailed and accurate study of the microcirculation. The present study examined the renal microvasculature of the rainbow trout, Salmo gairdneri. The conventional picture of a glomerulus with one afferent arteriole was common, but glomeruli were often supplied by two afferent arterioles. In the majority of these, the intrarenal artery gave rise to a single afferent arteriole that branched to form two smaller vessels before reaching the glomerulus. Glomeruli with two afferent arterioles that arose independently from the intrarenal artery also occurred. The majority of glomeruli had a single efferent arteriole, but a proportion of glomeruli had two efferent arterioles. Efferent arterioles were smaller in diameter than the afferent arterioles. The glomerular capillaries were arranged in lobules, with few anastomoses between lobules, so that, for glomeruli with two afferent or two efferent arterioles, vascular perfusion and thus filtration within discrete lobules is probable.     

Flow resistance of the interlobular artery in the rat kidney

The afferent and efferent arterioles are considered to be the most important resistance vessels within the renal vasculature, but there are indications that a pressure drop occurs along the interlobular artery. This pressure drop was investigated from two aspects: 1) In rat kidneys the “stop-flow pressure” in the efferent arterioles was measured with the micropuncture technique. At arterial pressures between 100 and 130 mmHg the stop-flow pressure did not exceed 85 mmHg, which means that the highest pressure at the end of the interlobular artery was 85 mmHg; 2) A mathematical model was constructed, assuming that the diameter of the interlobular artery decreased stepwise from 60 to 10/μm. The artery was divided into 20 segments, each segment containing one afferent arteriole. The flow in the afferent arterioles increased linearly from 100nl · min^-1 in the first segment to 130nl · min^-1 in the last segment. When the pressure in the first segment was 120 mmHg, it was calculated that the pressure in the last segment was 85 mmHg. These findings strengthen the theory that the interlobular artery may participate in the regulation of the intracortical blood flow in the rat kidney. We conclude that the afferent arteriole of the most superficial nephron is nearly maximally dilated and that the juxtamedullary nephron is able to either dilate or constrict its arteriole in normotensive and normohydrated rats.     

Intrarenal blood flow distribution in the desert quail following salt loading.

The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation.     

Renal vasculature of the trout demonstrated by scanning electron microscopy,compared with canine glomerular vessels

In order to gain additional information regarding renal circulatory patterns, we have used both ink and resin injections to study the arterial supply to the mesonephric kidney of trout. Arterial injections through the dorsal aorta with ink were made for histological preparations in which the length, termination and relationship of glomerular vessels were examined. Similar injections with methyl methacrylate were made in preparation of corrosion casts to provide us with gross replicas of the aortic branches to the kidney as well as casts of glomerular structure for scanning electron microscopy. The sequence of vessels through which arterial blood passed to the renal corpuscle and ultimately to the uriniferous tubules was traced. Each afferent arteriole was found to terminate in three to six brancehs which formed anastomosing circuits of capillaries; these vessels reunited at the hilum to form a single efferent arteriole. The efferent arterioles in turn traveled a short distance to peritubular capillary beds and sinusoids. Morphological evidence was found for preglomerular sphincter-like action only. The glomerular vessels were found to be similar to, although less complex than, those of the outer and mid-cortical regions of the dog kidney.     

The tubulo-glomerular feedback mechanism — a determinant for the autoregulation of the glomerular filtration rate in superficial and juxtamedullary nephrons

Summary The intrinsic myogenic hypothesis and the tubuloglomerular feedback mechanism (TGF) give the presently most cherished explanation to the autoregulation of renal blood flow and glomerular filtration rate. A series of experiments was performed on young, normohydrated rats in order to evaluate the importance of TGF as an autoregulatory factor of the single nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephron populations. Micropuncture techniques were applied to tubular structures of the renal surface and on the papilla for the measurement of hydrostatic pressures and SNGFR. The SNGFR was also measured with a modified Hanssen technique. A TV-technique was used to record the urine free flow rate in the loop of Henle.The net driving forces for glomerular filtration at the afferent end of the glomerular capillaries were estimated to be 19 and 47 mm Hg for superficial and juxtamedullary nephrons respectively, when the urine flow at the macula densa was zero. The SNGFR of the two nephron populations amounted to 29.6 and 84.1 nl·min^–1·g^–1 K.W., as measured with the micropuncture technique. With a modified Hanssen technique the corresponding values were 25.8 and 27.7 nl·min^–1. g^–1 K.W. (kidney weight).The SNGFR was found to be well autoregulated when the urine flow at the macula densa was intact, but not when the urine flow was interrupted.The flow rate in the loop of Henle was in free flow conditions 7.3 nl·min^–1·g^–1 K.W. which shall be compared with 19.2 nl·min^–1·g^–1 K.W. when the urine flow to the macula densa was zero.We conclude that SNGFR is mainly autoregulated by the TGF-mechanism in young, normohydrated rats at lower arterial pressures. In normal conditions TGF is highly activated for juxtamedullary nephrons, but not for the superficial ones. The high urine flow rate in the loop of Henle at reduced flow rates at the macula densa may invalidate the use of loop blockade in studies of water and solute transfer across the loop walls.     

Afferent arteriolopathy and glomerular collapse but not segmental sclerosis induce tubular atrophy in old spontaneously hypertensive rats

In chronic renal disease, the temporal and spatial relationship between vascular, glomerular and tubular changes is still unclear. Hypertension, an important cause of chronic renal failure, leads to afferent arteriolopathy, segmental glomerulosclerosis and tubular atrophy in the juxtamedullary cortex. We investigated the pathological changes of hypertensive renal disease in aged spontaneously hypertensive rats using a large number of serial sections, where we traced and analyzed afferent arteriole, glomerulus and proximal tubule of single nephrons. Our major finding was that both afferent arteriolopathy and glomerular capillary collapse were linked to tubular atrophy. Only nephrons with glomerular collapse (n = 13) showed tubules with reduced diameter indicating atrophy [21.66 ± 2.56 μm vs. tubules in normotensive Wistar Kyoto rats (WKY) 38.56 ± 0.56 μm, p < 0.05], as well as afferent arteriolar wall hypertrophy (diameter 32.74 ± 4.72 μm vs. afferent arterioles in WKY 19.24 ± 0.98 μm, p < 0.05). Nephrons with segmental sclerosis (n = 10) did not show tubular atrophy and tubular diameters were unchanged (35.60 ± 1.43 μm). Afferent arteriolar diameter negatively correlated with glomerular capillary volume fraction (r = −0.36) and proximal tubular diameter (r = −0.46) implying reduced glomerular and tubular flow. In line with this, chronically damaged tubules showed reduced staining for the ciliary protein inversin indicating changed ciliary signalling due to reduced urinary flow. This is the first morphological study on hypertensive renal disease making correlations between vascular, glomerular and tubular components of individual nephron units. Our data suggest that afferent arteriolopathy leads to glomerular collapse and reduced urinary flow with subsequent tubular atrophy.     

Adaptive changes of juxtamedullary glomerular filtration in the remnant kidney

The participation of surviving juxtamedullary nephrons in the adaptive changes of glomerular filtration that occur in response to loss of functioning nephron mass was examined by direct micropuncture of the rat renal papilla. The solitary remnant kidney (RK) in rats with an 85% reduction of renal mass demonstrated strikingly elevated values for single nephron glomerular filtration rate (SNGFR) in both superficial (46.1±3.2 nl/min) and juxtamedullary (73.5±6.1 nl/min) nephrons in comparison to respective values observed in normal hydrophenic rats (superficial SNGFR=15.0±1.9nl/min,P<0.001, and juxtamedullary SNGFR=30.2±3.2 nl/min,P<0.001). In RK rats, the proximal portions of both superficial and juxtamedullary nephrons exhibited a marked increase in absolute fluid reabsorption as well as a markedly enhanced delivery of fluid to more distal portions of the nephron. These observations indicate that similar, not preferential, functional adaptations in glomerular filtration occur concommitantly in both superficial and juxtamedullary nephrons consequent to reduction of renal mass.     

Structure of the amphibian mesonephric tubule during ontogenesis in Rana ridibunda L. tadpoles: early ontogenetic stages, renal corpuscle formation, neck segment and peritoneal funnels

The morphological changes produced in the mesonephric tubule during ontogenesis, not previously reported in amphibians, are described in Rana ridibunda tadpoles using light and electron microscopic methods. The rudimentary nephron units do not develop synchronously along the subperitoneal nephrogenic ridged cord. The first signs of morphogenesis are the presence of round euchromatinic nuclei and mitotic figures. The subsequent developmental stages are characterized by detachment of the rudimentary nephrons from the nephrogenic cord. Renal corpuscle formation is characterized by glomerular expansion, differentiation of large fenestrated capillaries and the presence of a discrete mesangium and a small capsular space. Interstitial capillaries next to the renal corpuscle rudiments appear to induce invagination and differentiation of the capsular epithelium. Developing podocytes were cuboidal undifferentiated epithelial cells with scarce primary processes and with an extensive part of the cell surface lying flat on the glomerular basement membrane. These features reflect low or no glomerular filtration during nephron development. The ciliated neck segment and peritoneal funnels show similar structural features. The latter were not physically connected with the nephrons, but opened into renal blood vessels. Involutive peritoneal funnels were observed.     

Effect of isotonic volume expansion on glomerular filtration rate and renal hemodynamics in the developing rat kidney

Young rats (20–24 days) and adult rats (4–5 days) were studied during hydropenia and volume expansion with regard to glomerular filtration rate (GFR) and the determinants of GFR. During hydropenia, GFR and renal blood flow (RBF) were significantly lower in younger than in adult rats both in absolute terms and when related to bodyweight. Equivalent degrees of volume expansion (6% of b. wt.) resulted in a much more pronounced increase in GFR and RBF in younger than in older rats. This suggests that the high renal vascular resistance in hydropenic young rats is primarily due to vasoconstriction. The relationship between the filtration rate of superficial nephrons and the total GFR was the same in hydropenic and volume expanded rats in both age groups. The tubular stop flow pressure, the calculated hydrostatic glomerular capillary pressure and ultrafiltration pressure in the afferent part of the glomerular capillaries was slightly lower in hydropenic young rats than in hydropenic adult rats. The pressures did not rise after volume expansion. It is concluded that the marked increase in GFR in volume expanded young rats is mainly due to increased renal plasma flow.