Direct measurement of papillary collecting duct sodium transport in the rat. Evidence for heterogeneity of nephron function during Ringer loading.

It has been suggested that collecting duct sodium transport was inhibited by extracellular volume expansion. To directly evaluate this possibility, micropuncture of the papillary collecting duct of young rats was performed during hydropenia and Ringer loading. The possibility of heterogeneity of nephron function was evaluated during Ringer and hyperoncotic albumin loading by comparing the delivery of sodium to the end of the distal tubule of superficial nephrons with papillary base delivery. During hydropenia (n = 14), sodium delivery to the base averaged 0.95% of the filtered sodium load and reabsorption along the collecting duct was noted from base to tip in each collection pair averaging 0.80% of the filtered load. During Ringer loading, sodium delivery to the base was markedly greater than in hydropenia, 11.8 vs. 0.95% of the filtered load (P less than 0.001). Yet, sodium reabsorption was also much greater, 6 vs. 0.8% (P less than 0.001). In 13 paired collections, during Ringer loading, sodium delivery to the papillary base, 12.2% of the filtered load, was consistently greater than late distal tubular delivery from superficial nephrons. 8% (P less than 0.005). In contrast, reabsorption of sodium from late distal tubule to papillary base was found during albumin infusion, 6.2 vs. 3.1% (P less than 0.001). Therefore, these studies demonstrate that: (a) the delivery of sodium to and reabsorption along the papillary collecting duct were markedly greater during Ringer loading than in hydropenia; (b) the amount of sodium delivered to the papillary base was greater than the delivery to the end of the distal tubule of superficial nephrons during Ringer loading, suggesting that deeper nephrons deliver more sodium to the collecting duct in this setting; and (c) the difference in sodium excretion between Ringer loading and hyperoncotic albumin infusion is due to events occurring between the late distal tubule of superficial nephrons and the base of the papillary collecting duct.

Further studies on segmental sodium transport in the rat kidney during expansion of the extracellular fluid volume.

The present studies were designed to further investigate the possibility of heterogeneity of nephron function during Ringer loading in the rat, and to determine the specific nephron segment responsible for this finding. As in previous studies from this laboratory with smaller rats (50-125 g), net addition of sodium between late distal tubule and papillary base (6.9 vs. 10.4% of the filtered load, respectively, P <0.005) was found in more mature rats (170-230 g). In contrast, there was net reabsorption of sodium between these two segments in nonvolume-expanded animals, 1.70 vs. 0.45% of the filtered sodium load, P <0.005. Because nephron heterogeneity of sodium transport during extracellular volume expansion is the most likely explanation for these findings, further studies were performed to determine the specific juxtamedullary nephron segment responsible for the net addition pattern between late distal tubule and papillary base in Ringer-loaded animals. First, a comparison was made of sodium delivery to the late proximal tubule of superficial nephrons vs. the delivery rate to the bend of Henle's loop of juxtamedullary nephrons in both hydropenia and Ringer loading. Fractional sodium delivery was quite comparable between the superficial and juxtamedullary nephrons in both hydropenia and Ringer loading although the absolute level was much greater in both groups of nephrons in the Ringer studies. Chlorothiazide (15 mg/kg loading and 15 mg/kg per h) given during Ringer loading markedly increased late distal sodium delivery, 19% of the filtered load, but did not prevent net addition of sodium at the papillary base. In contrast, furosemide (5 mg/kg loading and 5/mg/kg per h) given during Ringer loading completely reversed the segmental pattern, 35.5 and 28.8% at late distal tubule and papillary base, respectively, P <0.005. These studies demonstrate that the net addition of sodium between late distal tubule and papillary base during Ringer loading is not limited to immature rats and that the segmental pattern does not occur in non-volume-expanded animals. Further, the reversal of the net addition pattern with furosemide, but not chlorothiazide, and the comparable proximal nephron delivery rates in Ringer loading suggest that the loop of Henle of juxtamedullary nephrons reabsorbs less sodium than the same portion of superficial nephrons in this setting. A model is proposed to explain this finding.

A comparison of the segmental analysis of sodium reabsorption during Ringer's and hyperoncotic albumin infusion in the rat.

Studies were designed to compare the segmental analysis of sodium reabsorption along the nephron during volume expansion with either 10% body weight Ringer's or 0.6% body weight hyperoncotic albumin. Total kidney and nephron glomerular filtration rate increased similarly with both, but urinary sodium excretion (12.7 vs. 4.0 mueq/min, P < 0.001) and fractional sodium excretion (5.0 vs. 1.6%, P < 0.001) increased to a greater extent with Ringer's. Fractional reabsorption of sodium in the proximal tubule was diminished in both groups but to a significantly greater extent during Ringer's (P < 0.005). Absolute reabsorption was inhibited only in the Ringer's group. Delivery of filtrate out of the proximal tubule was greater in the Ringer's studies, 45 vs. 37 nl/min (P < 0.001). However, both fractional and absolute sodium delivery to the early and late distal tubule were not significantly different in the two groups. Fractional reabsorption in the collecting duct decreased from 96% in hydropenia to 31% during Ringer's but fell only slightly to 80% in the albumin studies. Absolute collecting duct reabsorption was also greater in the albumin studies, 0.55 vs. 0.21 neq/min (P < 0.001), which could totally account for the difference in urinary sodium excretion between the two groups. (22)Na recovery in the final urine after end distal microinjections was 71% during Ringer's infusion and 34% during albumin (P < 0.001). From these data we conclude that: (a) Ringer's solution has a greater inhibitory effect on proximal tubular sodium reabsorption, and (b) in spite of this effect, differences in mucosal to serosal collecting duct sodium transport are primarily responsible for the greater natriuresis during Ringer's infusion.

The measurement of nephron filtration rate and absolute reabsorption in the proximal tubule of the rabbit kidney.

Micropuncture studies were performed in the rabbit to determine nephron filtration rate and absolute fluid reabsorption in the proximal tubule in order to compare the latter value with data obtained with the in vitro microperfusion technique. New Zealand white rabbits, 2-2.8 kg, were studied. Nephron filtration rate was 21 nl/min (n equal to 48) and absolute reabsorption along the length of the accesible portion of the proximal convoluted tubule was 10.3 nl/min. Correcting this value for tubular length gives a fluid reabsorption of approximately 1.9 nl/mm per min. In view of the marked difference between the in vivo and in vitro techniques and the various sources of error with each, this is reasonably similiar to the value of 1.3 nl/mm per min obtained in the isolated proximal convoluted tubule.

Studies on the mechanism of reduced urinary osmolality after exposure of renal papilla.

Studies were performed in Munich-Wistar rats to determine whether changes in papillary plasma flow might be responsible for the concentrating defect which occurs after exposure of the extrarenal papilla. Papillary plasma flow was measured by (125)I-albumin accumulation. Initial studies in hydropenic animals revealed that papillary plasma flow was 40% higher in the kidney with the exposured papilla, 41 vs. 29 ml/min per 100 g of papilla (P < 0.001). This increase in papillary plasma flow was detectable 15 or 45 min after removing the ureter. Because it was unclear whether the rise in papillary plasma flow was a cause or the result of the fall in urine osmolality, similar studies were performed in animals undergoing a water diuresis. In this setting, papillary plasma flow still increased on the exposed side compared to the control side, 81 vs. 60 ml/min per 100 g, despite similarly low urine osmolalities of 155 and 174 mosmol/kg, respectively. This finding is compatible with the possibility that papillary exposure per se causes an increase in papillary plasma flow and that this hemodynamic alteration may lead to a reduction in urinary osmolality secondary to washout of the medullary interstitium. A final group of hydropenic rats was given either indomethacin or meclofenamate before removing the ureter. In these studies, there was no difference in either the papillary plasma flow or the urine osmolality between control and exposed kidneys. It is therefore suggested that opening the ureter induces an increase in papillary plasma flow by some mechanism which may involve an alteration in prostaglandin synthesis.

The effect of bradykinin on proximal tubular sodium reabsorption in the dog: evidence for functional nephron heterogeneity.

In a previous study we have found that acetylcholine, a renal vasodilator, inhibits fractional and absolute reabsorption of sodium in the proximal tubule of the dog. To delineate whether this effect on proximal tubular sodium reabsorption was related to alterations in renal hemodynamics or to a direct tubular action of the drug, free-flow micropuncture studies were performed in the dog in which the tubular fluid to plasma inulin ratio and nephron filtration rate were determined before and during the administration of a structurally different renal vasodilator, bradykinin. This agent increased sodium excretion from 12 to 96 muEq/min and decreased total kidney filtration fraction from 0.35 to 0.25. However, sodium reabsorption in the proximal tubule of the superficial nephrons was unchanged during bradykinin administration. Since it has been shown that a decrease in filtration fraction and presumably peritubular capillary protein concentration will decrease proximal tubular sodium reabsorption, studies were performed to determine whether the fall in total kidney filtration fraction seen with both vasodilators is paralleled by a similar change in the circulation of superficial nephrons. The results of these studies indicate that neither agent altered superficial nephron capillary protein concentration, hematocrit, or filtration fraction. In contrast, a decrease in capillary protein concentration, hematocrit, and filtration fraction was consistently demonstrated during the intrarenal infusion of 7.5-15 ml/min of Ringer's solution while an increase in these parameters occurred during the i.v. administration of norepinephrine, 60 mug/min. In the Ringer's infusion studies, both fractional and absolute sodium reabsorption in the proximal tubule were decreased concomitant with the fall in capillary protein concentration and hematocrit. THIS DATA SUGGESTS THAT: (a) the hemodynamic effect of renal vasodilatation is not the same in the circulation of all nephrons; (b) the inhibitory effect of acetylcholine on proximal tubular sodium reabsorption is due to a direct tubular action; (c) a decrease in capillary protein concentration and/or hematocrit does decrease proximal tubular sodium reabsorption; (d) although proximal reabsorption of sodium is unchanged in the superficial nephrons during bradykinin administration, a decrease in reabsorption may be present in deeper nephrons in which filtration fraction is decreased.

Effect of renal vasodilatation on the distribution of cortical blood flow in the kidney of the dog.

Studies were performed to evaluate the validity of using the radioactive microsphere technique to measure regional blood flow in the renal cortex. A technique was developed in which the renal cortex was divided into four equal zones, and the fractional and absolute distribution of blood flow in these zones was determined. It was consistently found that approximately 70% of the renal blood flow was distributed to the two outer cortical zones with the remaining 30% going to the two inner cortical zones. In addition, there was a reproducible pattern of distribution of blood flow in different areas of the same kidney after a single injection of microspheres and in the same area of the kidney after multiple injections of microspheres. Using this method, the distribution of renal blood flow was determined before and during the intrarenal administration of either acetylcholine (40 mug/min) or bradykinin (5 mug/min). Both agents decreased the per cent of blood flow to outer cortical zone 1, caused no change in zone 2, and increased the fractional blood flow in inner cortical zones 3 and 4. When this data was evaluated in terms of total blood flow, there was no change in zone 1, an increase in zone 2 commensurate with the change in total blood flow, and a marked increase in inner cortical zones 3 and 4 which accounted for 60 and 65% of the increase in total blood flow during acetylcholine and bradykinin administration, respectively.Therefore, the natriuresis of renal vasodilatation is associated with a redistribution to inner cortical nephrons.

Studies of the mechanism of oliguria in a model of unilateral acute renal failure.

To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 mug/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringer's solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-muM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.

Increased urinary excretion of endothelin during hypothermic perfusion preservation in kidneys subjected to preretrieval warm ischemic injury.

The purpose of the study was two-fold: 1) to determine whether endothelin (ET) levels could be detected in the ureteral effluent during hypothermic perfusion preservation (HPP) and; 2) to determine whether preretrieval warm ischemic (WI) injury is associated with increased ureteral excretion of ET. In situ pre-WI injury was induced in Lewis rats (n=10) by a 30-min extrinsic occlusion of the suprarenal aorta. The left kidney underwent 16 hr of HPP, and ureteral effluent (UE) from ischemic and control kidneys (n=10) was collected over 16 hr of HPP. The UE ET concentration and total ET excretion over 16 hr of HPP were significantly higher in kidneys subjected to pre-WI injury compared with nonischemic controls. Kidneys subjected to pre-WI injury can be distinguished from nonischemic control kidneys during HPP by a significantly higher concentration of ET in the UE and a higher overall excretion of ET during HPP.

Identification of kidneys subjected to preretrieval warm ischemic injury by simultaneous monitoring of glomerular filtration and perfusate flow during hypothermic perfusion preservation.

BACKGROUND: Historically, ex vivo physiological evaluation of cadaveric renal allografts has been limited to assessing perfusate flow (PF) during hypothermic perfusion preservation (HPP). Using a small animal model, we have previously described a method for continuous monitoring of glomerular filtration rate (GFR) during HPP. Our study was undertaken to determine if monitoring GFR and PF during HPP distinguished kidneys subjected to preretrieval warm ischemic (WI) injury more reliably than PF alone. METHODS: In situ WI was induced in Lewis rats (n=10) by extrinsic occlusion of the suprarenal aorta for 30 min. After in situ cold perfusion and retrieval, the left kidney underwent 16 hr of HPP. Nonischemic (NI) control kidneys (n=10) were retrieved in the absence of suprarenal aortic occlusion. Longitudinal changes in PF, GFR, and filtration fraction (FF) during HPP were compared in WI versus NI kidneys (FF=GFR/PF x 100%). RESULTS: PF remained the same in both cohorts throughout HPP. GFR, however, increased to a significantly greater degree in WI versus NI kidneys during the first 4 hr of HPP (713+/-401 vs. 26+/-23%, respectively) (P<0.05). The increase in FF at 4 hr was 1203+/-696% in the WI kidneys versus 83+/-46% in the NI controls (P<0.05). CONCLUSIONS: In contrast to PF alone, measurement of both PF and GFR distinguished kidneys subjected to pre-WI from NI controls. The data provide a means to determine if monitoring of both GFR and PF during HPP will predict short- and long-term renal allograft function more reliably than PF alone.

Tubular site(s) of action of atrial natriuretic peptide in the rat.

With micropuncture techniques, the present study examined the delivery of chloride to the superficial late distal tubule and the base and tip of the papillary collecting duct in rats treated with either Wy 47663, a synthetic analogue of atrial natriuretic peptide (ANP), or vehicle alone. Whole kidney glomerular filtration rate (GFR) and single-nephron glomerular filtration rate were not significantly different between the two groups. Late distal tubule chloride delivery was also not different between ANP- (5.71 +/- 1.15%) and vehicle- (6.28 +/- 1.12%) treated animals. However, fractional delivery to the base of the papillary collecting duct was significantly greater in the ANP-treated rats (14.37 +/- 1.98%) compared with vehicle-treated rats (7.32 +/- 1.47%). Tip papillary collecting duct delivery was also significantly greater in the ANP-treated rats (1.97 +/- 1.96 vs. 3.09 +/- 0.60%). In addition, the percent of chloride delivered that was reabsorbed along the papillary collecting duct was significantly less in the ANP-treated rats. In conclusion, ANP inhibits reabsorption in some tubular segments between the superficial late distal tubule and papillary collecting duct base as well as in the accessible portion of the papillary collecting duct.

Methodologic considerations in the study of glomerular ultrafiltration.

Over the past decade numerous studies have detailed the dynamics of glomerular ultrafiltration. Observations in a unique strain of Munich-Wistar rats, which afford the direct measurement of intraglomerular capillary hydrostatic pressure, have determined that under normal physiologic conditions these animals are in a state of filtration equilibrium. Both mathematical models based on this observation and experimental evidence indicate that under these circumstances the primary determinant of glomerular filtration rate (GFR) is the rate of glomerular plasma flow. In addition, this state of filtration equilibrium provides a condition in which changes in the product of glomerular surface area and glomerular capillary hydraulic conductivity (ultrafiltration coefficient) have no influence on glomerular filtration rate. Similarly, changes in glomerular hydrostatic pressure have a relatively small influence on GFR. These conclusions represent a marked alteration of the previously held concepts of the determinants of GFR. Unfortunately, studies in other strains of rats and in other animal species, particularly the dog, have led to the conclusion that filtration disequilibrium is the normal physiologic condition. The validity of this conclusion, however, is made uncertain by methodologic necessities that may lead to erroneous physiologic measurements of the determinants of GFR. In the present Editorial Review we examine the data reflecting on the applicability of filtration equilibrium to mammalian species. In addition, we summarize two new in vitro techniques for the further study of the dynamics of glomerular ultrafiltration.

Pathophysiology of a nephrotoxic model of acute renal failure.

Studies were performed in the dog to determine the mechanism of the renal functional impairment which follows the administration of the nephrotoxic agent, uranyl nitrate. In the first series of 28 experiments, total renal blood flow was determined with the radioactive microsphere method before and after uranyl nitrate administration, 10 mg/kg. Total blood flow fell from 199 to 121 ml/min 6 hr after administration of uranyl nitrate (P less than 0.001) but was unchanged 48 hr after administration of the drug. Yet the blood urea nitrogen concentration had increased from a control value of 13 to 120 mg/100 ml at 48 hr (P less than 0.001). Since renal blood flow was normal at 48 hr, micropuncture studies were performed to further evaluate the mechanism of the renal impairment. In the first group of nine studies using a 10 mg/kg dose of uranyl nitrate, nephron glomerular filtration rate (GFR) was reduced 37% while total kidney GFR averaged less than 1% of normal. A similar disparity between superficial and total GFR was noted after a 5 mg/kg dose even though urine flow was comparable to values found in normal hydropenic dogs. Proximal tubular transit time and intratubular pressure were normal. The recovery of 3H-inulin injected into the proximal tubule was 97% in normal dogs and 14% in uranyl nitrate dogs (P less than 0.001). Since there was no difference between early and late proximal tubular nephron GFR, it was suggested that the pars recta, the segment most severely involved histologically, was the main site of inulin leak. Scanning electron microscopy revealed an alteration in epithelial architecture which may have accounted, at least in part, for the diminution in nephron GFR. These studies are interpreted to indicate that the impairment in renal function in this model is due to both leakage of filtrate across damaged tubular epithelium and a modest decrease in nephron GFR.

Effect of aortic clamping on proximal reabsorption and sodium excretion in the rat.

It has been suggested that aortic clamping prior to expansion of the extracellular fluid volume prevents the natriuretic response normally seen in this setting. To further evaluate this finding, two groups of re-collection micropuncture studies were performed before and after 7.5% body wt expansion with Ringer solution. Group I, immediate-clamp studies, n, 11. After control collections, perfusion pressure to the left kidney was decreased to 75 mmHg followed by Ringer loading. Group II, delayed-clamp studies, n, 8. After control collections, Ringer solution was given for 40 min. Then the left renal perfusion pressure was reduced to 75 mmHg and the Ringer infusion was continued at the same rate. In the immediate-clamp group, there was no change in total kidney glomerular filtration rate (GFR) (1.16 vs. 1.11 ml/min), nephron GFR (40 vs. 39 nl/min), tubular fluid-to-plasma inulin ratio (2.40 vs. 2.28), or filtrate delivery out of the proximal tubule (18 vs. 18 ndium excretion were not significantly altered. In the delayed-clamp studies, there was also no change in total or nephron GFR, but the tubular fluid-to-plasma inulin ratio fell from 2.52 to 1.65 (P less than .001) and distal delivery rose 9 nl/min after expansion (P less than .001). Sodium excretion increased 3.83 mueq/min and fractional sodium excretion rose 2.28%, both values being markedly greater than in the immediate-clamp studies (P less than .005 for both). These results demonstrate that immediate clamping obviates the fall in proximal reabsorption and the natriuretic response to Ringer loading and suggests that intrarenal adjustments are a major determinant of the magnitude of the natriuretic response to expansion of the extracellular volume

Potassium transport in the distal tubule and collecting duct of the rat.

Because of recent conflicting results, micropuncture studies were performed to clarify the respective role of the distal convoluted tubule and collecting duct in the regulation of urinary potassium excretion. Five groups of Sprague-Dawley rats were studied: group I, hydropenia (n = 10); group II, Ringer loading (n = 7); group III, acute KC1 loading (n = 6); group IV, mannitol diuresis (n = 6); group V, KC1 infusion during mannitol diuresis (n = 7). Early and late distal tubules were identified with intravenous injections of lissamine green. In each animal net secretion of potassium occurred along the distal convoluted tubule, and a direct relationship between distal tubular flow rate and potassium secretion was observed. The magnitude of potassium secretion at high distal tubular flow rates was dependent on the model studied. Potassium transport beyond the distal tubule was evaluated by comparing end distal potassium delivery and fractional potassium excretion. At low urinary flow rates net reabsorption was observed, whereas at higher flow rates no net transport occurred. Thus, flow rate along the collecting duct may be a major determinant of urinary potassium excretion.

Measurement of renin secretion in single perfused rabbit glomeruli.

A new technique is presented that allows the measurement of the renin secretion rate of single rabbit glomeruli during in vitro perfusion at controlled afferent arteriolar perfusion pressure. Rabbit glomeruli with intact afferent arteriole and Bowman's capsule are obtained by microdissection and cannulated with a pipette system that allows continuous afferent arteriolar pressure measurement. The renin secretion rate of 10 glomeruli, perfused at 40 mmHg, was measured in 15-min intervals with an antibody-trapping microassay. Renin secretion rate was low relative to total renin content (1.2-2.0% of content/perfusion h) and increased three- to fivefold in response to isoproterenol (10(-5) M). The afferent arteriole contracted to norepinephrine (10(-5) M) in each instance. This novel, although difficult, technique allows the study of renin release in vitro at controlled perfusion pressure, without the interfering effects of the macula densa, arterial angiotensin II, and the adrenergic nervous system. It should allow a new perspective on issues such as the pressure-flow dependence of renin release and the interaction of the afferent arteriolar endothelium with the renin-secreting juxtaglomerular cells.

Alterations in vascular function and morphology in acute ischemic renal failure.

Left renal arteries of rats were clamped for 40 min, and the kidneys were studied 48 hr and 7 days following restoration of blood flow. At 48 hr, there was severe oliguria or anuria. Renal blood flow (RBF) was in the normal range, but there was a loss of RBF autoregulation between 95 to 120 mm of mercury in seven out of nine rats. Morphologically, arcuate and interlobular arteries and afferent arterioles showed focal, segmental necrosis of smooth muscle cells and diapedesis of red blood cells across their walls. At 7 days, renal function was still severely depressed. RBF showed a slight decrease that did not reach statistical significance, and RBF autoregulatory capacity was lost in 8 out of 11 rats. Morphologically, vascular lesions were characterized at this stage by marked thickening and fibrosis of the tunica adventitia of the interlobular arteries and afferent arterioles. Structural vascular alterations may impair smooth muscle contractile function and thus interfere with RBF autoregulatory function in this model of acute renal failure.

Effect of albumin on glomerular ultrafiltration coefficient in isolated perfused dog glomerulus.

To evaluate the direct effect of albumin concentration on the glomerular capillary ultrafiltration coefficient (Kf), we compared the effect of "normal" (3.4 g/100 ml), "low" (0.1 g/100 ml), and "no albumin" (less than 0.005 g/100 ml) concentration on the determinants of single-nephron glomerular filtration rate (SNGFR) as measured with the isolated perfused glomerulus technique. When the albumin concentration was decreased from normal to low concentrations, the afferent flow rate increased from 318 +/- 147 (mean +/- SE) to 450 +/- 174 nl/min, the filtration fraction increased from 0.19 +/- 0.04 to 0.35 +/- 0.08, and the SNGFR increased from 49 +/- 21 to 126 +/- 34 nl/min. These changes were associated with a small though significant increase in Kf from 2.79 +/- 1.01 to 3.74 +/- 0.98 nl/(min X mmHg) (P less than 0.05). When the albumin concentration was decreased from low to no albumin the filtration fraction and SNGFR increased even further and were associated with a marked increase in Kf to a value of 27.04 +/- 11.43 nl/min X mmHg). We conclude that there is very little effect of decreases in albumin concentration on Kf until extremely low levels are reached, and at that point there is a marked increase in the ultrafiltration coefficient. Furthermore, when these extremely low concentrations of albumin are reached an important role for albumin in the basic function of the ultrafiltration barrier is demonstrable.

Effect of atriopeptin II on determinants of glomerular filtration rate in the in vitro perfused dog glomerulus.

Atrial natriuretic factor (ANF) is a peptide originally found to be present in extracts of mammalian atria that possess marked natriuretic and diuretic qualities. A number of mechanisms have been suggested to explain these properties. Recently, it has been suggested that ANF may enhance glomerular filtration. In this report, we describe a series of experiments designed to investigate if atriopeptin II, a 23-amino acid synthetic analogue of ANF, increases glomerular filtration rate (GFR) and, if so, the mechanism for this increase. We used the isolated perfused glomerulus technique (n = 6), which allows a single isolated glomerular unit to be perfused and the determinants of single-nephron GFR (SNGFR) to be measured. Two periods were performed in each experiment, the control followed by the experimental. The only difference between the two periods was the addition of atriopeptin II to the experimental perfusate at a final concentration of 5 X 10(-7) M. There was indeed a significant increase in the SNGFR (78 +/- 27 to 108 +/- 29 nl/min, P less than 0.01). This increase was associated with a significant increase in the glomerular capillary hydrostatic pressure (PGC) from 31 +/- 3 to 35 +/- 3 mmHg (P less than 0.05). The filtration fraction also increased in each experiment (from 0.16 +/- 0.3 to 0.25 +/- 0.03, P less than 0.005). Neither the afferent flow nor the efferent arteriolar flow changed, although there was a tendency for both to decrease.(ABSTRACT TRUNCATED AT 250 WORDS)