Tubular function by lithium clearance, plasma amino acids and hormones following a meat meal in childhood.

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90 min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30 min. The mean baseline CLi was 23.1 +/- 1.64 ml/min/1.73 m2. At peak GFR response (60 min from starting the meal), CLi averaged 27.6 +/- 2.4 ml/min/1.73 m2 (p less than 0.025 vs. baseline) and it was further increased (32.2 +/- 5.04 ml/min/1.73 m2, p less than 0.01 vs. baseline) 120 min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 +/- 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 +/- 0.07 (p less than 0.025 vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 +/- 780 versus 3,200 microM at baseline, p less than 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: A Micropuncture Study of HCO3 Reabsorption by the Hypertrophied Proximal Tubule

In rats with renal failure produced by excision of one kidney and infarction of large portions of the other kidney, given a low calcium, high phosphorus diet for 2-3 weeks, GFR was reduced by 80 percent, the fractional excretion of sodium increased from 7 to 23 percent, that of bicarbonate from 16 to 23 percent and that of water from 4 to 13 percent. Single nephron GFR in the remaining nephrons was nearly doubled and end-proximal TF/P_In was depressed from 2.3 to 1.8, and proximal TF/P_HCO3 from 0.52 to 0.35, the latter figure corresponding to an increase of absolute proximal HCO₃ reabsorption from 1.7 to 3.5 nEq/min or from 2.8 to 3.2 Eq/L of single nephron glomerular filtrate. Acute parathyroidectomy had no influence on the fall of GFR or the rise of SNGFR in the remaining nephrons and failed to cause any significant changes in proximal tubular bicarbonate reabsorption. Parathyroidectomy, on the other hand, practically prevented the rise of the fractional excretion of sodium and of water and inverted the rise of the fractional excretion of bicarbonate to a fall. The data are interpreted to indicate that secondary hyperparathyroidism in renal failure impairs distal nephron bicarbonate and sodium reabsorption and, thus, contributes to the maintenance of sodium balance, but could possibly aggravate acidosis.     

A search for a defect of proximal transport in denervated kidneys of conscious dogs

The influence of renal nerves on proximal Na+ reabsorption was studied in clearance experiments with unilaterally renal-denervated conscious dogs prepared by surgical bladder division. Two types of experiments were made : A. maximal water diuresis, and B. Total blockade of distal NaCl reabsorption with ethacrynic acid and chlorothiazide. In maximal water diuresis CH2O + CNa was used as a measure of fluid delivery to the distal nephron. At similar GFR on both sides, the proximal reabsorption estimated as GFR--(CH2O + CNa) was 38.4 +/- 5.6 ml/min for the intact and 35.9 +/- 4.2 ml/min for the denervated kidney (n = 6, difference NS). After distal tubular blockade, proximal Na+ reabsorption calculated as filtered load minus urinary excretion was 3.84 +/- 0.43 mmol/min for the intact and 3.91 +/- 0.36 mmol/min for the denervated kidney (n = 6, difference NS). The fractional reabsorption of NA+ was 64.9 +/- 1.0% for the intact and 66.9 +/- 1.1% for the denervated kidney (difference NS). In contrast to data from renal denervation studies with anaesthetized animals, the present experiments did not show any difference in proximal reabsorption between the innervated- and denervated kidney. We conclude that in absence of anaesthesia renal efferent nerves have no major effect on NaCl transport in dog proximal tubule.     

A stop-flow study of intrarenal effects of atrial natriuretic factor

We performed paired series of stop-flow studies on six mongrel dogs to determine a possible nephron site of action of synthetic atrial natriuretic factor (ANF). The initial free-flow response to intrarenal infusion of 5 micrograms/min of synthetic ANF into mannitol-expanded dogs resulted in an increased urine flow rate (6.81 +/- 0.88 to 9.00 +/- 1.17 ml/min, P less than 0.05) and a 40% increase in sodium excretion (496 +/- 110 to 694 +/- 166 meq/min, P less than 0.025) when compared to paired control periods. Renal blood flow did not change, but the glomerular filtration rate increased 4% (47 +/- 5 to 49 +/- 6 ml/min, P less than 0.05). The filtered load of sodium increased 4% (P less than 0.05), and the fractional sodium excretion increased by 35% (P less than 0.01). Stop-flow experiments showed no difference in tubular sodium concentration or in the fractional sodium-to-inulin ratio at the nadir of sodium concentration, suggesting that no differences existed in distal tubular sodium handling. Further, no apparent differences were detected in collections representing the more proximal portions of the nephron. While we were able to demonstrate marked natriuresis in response to synthetic ANF, no tubular effect was discernible, and the natriuresis obtained appears to be predominantly a function of hemodynamic effects.     

Urinary excretion of cGMP in response to atrial natriuretic peptide in dogs with acute pancreatitis

Previous studies have shown that when atrial natriuretic peptide (ANF) is given to anaesthetized dogs with hypovolemic acute pancreatitis, it will produce a diuresis and natriuresis but will not elevate the glomerular filtration rate (GFR). When the same dose of peptide is given to dogs equally hypovolemic (hemorrhage) but without pancreatitis, a brisk increment in GFR occurs. GFR will, however, rise in dogs with pancreatitis in response to other peptides, such as glucagon. In these studies we assessed cGMP excretion as a marker for ANF effect in both normal anaesthetized dogs and dogs with acute experimental pancreatitis. In each group, urinary output and sodium excretion increased significantly, but GFR rose only in the control group. Urinary excretion of cGMP rose equally and dramatically in both control and experimental animals. We conclude that GFR is prevented from rising in dogs with experimental pancreatitis following ANF, but this effect does not depend on depressed cGMP generation.     

Role of increased glomerular filtration rate in atrial natriuretic factor-induced natriuresis in the rat

One of the major renal hemodynamic actions of atrial natriuretic factor (ANF) is to increase glomerular filtration rate (GFR). To assess the role of this effect on ANF-induced natriuresis (UNaV), diuresis (V) and kaliuresis (UKV) we performed late clamp experiments in six rats. After control periods (C), synthetic ANF (auriculin A) was infused i.v. (2 micrograms X min-1/kg body wt) throughout the experiment (150 min). After pre-clamp periods, the perfusion pressure of the left kidney (LK) was reduced to 75-80 mmHg. The right kidney (RK) served as a time control. In LK, before the late clamp, ANF increased (p less than 0.01) GFR from 1.5 +/- 0.1 to 1.8 +/- 0.1 ml/min, V from 17 +/- 5 to 53 +/- 5 microliters/min, and UNaV from 2.1 +/- 0.6 to 10.0 +/- 0.9 microEq/min. Almost identical increases occurred in the RK. The late clamp returned all parameters in LK to C values (p greater than 0.05): GFR to 1.4 +/- 0.1 ml/min, V to 6.3 +/- 1.2 microliter/min, and UNaV to 1.0 +/- 0.3 microEq/min. The late clamp also reversed the ANF-induced increase in UKV. In the RK, GFR (1.8 +/- 0.1 ml/min), V (38 +/- 4 microliter/min) and UNaV (7.8 +/- 0.8 microEq/min) remained elevated (p less than 0.01 vs. C) to the end of the experiment. These data demonstrate that upon return of GFR to control levels, the ANF-induced diuresis, natriuresis and kaliuresis is abolished. The results support our previous view that the increase in GFR together with a decrease in inner-medullary hypertonicity account wholly or in great part for the natriuretic action of ANF.     

Further observations on the response of the glomerular filtration rate to glucagon: comparison with secretin.

Glucagon causes marked elevations of glomerular filtration rate (GFR) in dogs when administered intravenously (i.v.) in small doses. The associated natriuresis is thought to be entirely due to increments in the filtered sodium load. In this study, renal denervation, thyroparathyroidectomy, and blockade of cholinergic, alpha- and beta-adrenergic, dopaminergic and histaminergic receptors did not prevent the usual glucagon-induced elevations of GFR or rate of sodium excretion (UNaV). This effect of glucagon was not mediated through the release of cyclic AMP, or by plasma compositional changes of Ca-2+, K+, or amino acids. Pure porcine secretin, in doses of 5--10 mug/min delivered either i.v. or into the left renal artery did not alter GFR; clearance of the p-aminohippurate (CPAH) or UNaV in either hydropenic or saline-loaded dogs. Nor did this polypeptide, structurally very similar to glucagon, abolish the effect of glucagon on GFR. It did, however, partially inhibit the glucagon-induced natriuresis, presumably by preventing a previously undetected glucagon action on tubular reabsorption of sodium.     

Fluoride reabsorption by nonionic diffusion in the distal nephron of the dog

This study was done to test the hypothesis that fluoride reabsorption is extensive from the distal nephron, the major site for tubular fluid acidification, and to compare the distal nephron handling of fluoride and chloride. Ten stop-flow studies were done in five dogs anesthetized with pentobarbital. Urinary alkalinization was achieved by the intravenous infusion of sodium bicarbonate and acetazolamide or lithium chloride. Acidification was achieved by the infusion of sodium nitrate or sodium sulfate. The results indicate that the extent of fluoride reabsorption from the distal nephron is inversely correlated with urinary pH (P less than 0.001). When the urine was strongly acidified by the infusion of sodium sulfate, urine to plasma fluoride concentration ratios were less than 1.0, a finding not previously reported from studies of the renal handling of fluoride. The reabsorption of fluoride from the distal nephron was not correlated consistently with that of chloride. The results indicate that the distal nephron is an important site for the reabsorption of fluoride and they provide additional evidence that HF is the permeating moiety.     

Regulation of glomerular filtration rate and sodium excretion by angiotensin II

In addition to its extrarenal functions, including the control of arterial pressure and aldosterone secretion, the renin-angiotensin system (RAS) also has multiple intrarenal actions in controlling glomerular filtration rate (GFR) and sodium excretion. Angiotensin II (AngII) helps to prevent excessive decreases in GFR in different physiological and pathophysiological conditions by preferentially constricting the efferent arterioles, an action that can be mediated by either intrarenally formed or circulating AngII. Circulating AngII and intrarenally formed AngII do not appear to directly constrict preglomerular vessels, including the afferent arterioles, when the RAS is activated physiologically. The sodium-retaining action of AngII may be due, in part, to constriction of efferent arterioles and to subsequent changes in peritubular capillary physical forces. However, AngII may also directly stimulate sodium reabsorption in proximal and distal tubules, although the exact site at which AngII increases distal tubular transport is still uncertain. Considerable evidence indicates that the direct intrarenal effects of AngII on tubular reabsorption, including those caused by changes in peritubular capillary physical forces or a direct action on tubular transport, are quantitatively more important than those mediated by changes in aldosterone secretion. Thus, the intrarenal effects of AngII provide a mechanism for stabilizing the GFR and excretion of metabolic waste products while causing sodium and water retention, thereby helping to regulate body fluid volumes and arterial pressure.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Effect of catecholamines on electrolyte and water transport in the nephron of lower vertebrates

Micropuncture technique and electron microprobe analysis have been used to investigate the role of noradrenalin in ion and water balance in the renal tubules of the lamprey Lampetra fluviatilis and newt Triturus vulgaris. Noradrenalin decreased Na, K, and Ca concentrations in the proximal lumen of the lamprey increasing the value of (TF/P)in from 1.1 +/- 0.1 to 1.3 +/- 0.1 (p less than 0.001). Regitin blocked these effects. Noradrenalin perfusion of the peritubular capillaries in newt kidney increased ion and water reabsorption in the proximal segment of the nephron and resulted in differential changes of ion transport in the distal tubule, increasing reabsorption of Na, Cl and K and inhibiting that of Ca and Mg. The rate of glomerular filtration in the nephron remained practically unaffected. The data obtained reveal direct effect of noradrenalin on the renal tubular function in lower vertebrates, this effect being realized presumably via alpha-adrenoreceptors.     

The effect of intravenous hypertonic saline infusion on renal function and vasopressin excretion in sheep.

Conscious Merino ewes were given an intravenous hypertonic sodium chloride load of 4 mmol.min-1 for 100 min. This resulted in increases in urine flow, sodium and potassium excretion and plasma sodium concentration and osmolality. Urinary vasopressin output and solute-free water reabsorption increased and plasma renin activity declined. Renal plasma flow and glomerular filtration rate (GFR) rose, as did the solute clearance. The change in urinary osmolality was related to the initial urine osmolality such that when the initial urine osmolality was high the urine became more dilute, and vice versa. Tubular sodium reabsorption increased but the fractional reabsorption rate fell. It is suggested that the increase in GFR was at least partly due to the increase in AVP and that the electrolyte loss can be accounted for by the increase in GFR without necessarily involving AVP or other hormonal effects at the tubular level.     

Effect of glucagon and glomerulopressin on the renal function of the dog.

Glucagon was infused through the porta or through the left renal artery in dogs. Another group of dogs were infused with glomerulopressin through the left renal artery. It was observed that glucagon when infused through the portal vein enhanced the glomerulopressin production and the glomerular filtration rate (GFR). When glucagon was infused intrarenally it did not alter GRF but it had a direct tubular action decreasing sodium reabsorption in the proximal tubule. Glomerulopressin infused intrarenally increased GRF and potassium excretion. The results suggest that the increase in GFR was due to increase in glomerulopressin activity. There are three reasons for this statement: a) GRF increased when glomerulopressin activity was high, but not when there was a low activity, 5) intrarenally infused glomerulopressin produced a very significant change in the GFR of the infused kidney, while the GRF of the contralateral kidney remained unchanged and c) intrarenally administered glucagon had no effect on GFR.     

Lack of anion effect on volume expansion natriuresis in the developing canine kidney

The renal response to volume expansion with sodium chloride or sodium bicarbonate was studied in 15 newborn and 13 adult dogs. Proximal and distal nephron function were estimated using the technique of distal nephron blockade. Fractional sodium reabsorption was 99.0 +/- 0.3% in newborn and 96.6 +/- 0.06% in adult during the NaCl expansion (P less than 0.01) and 98.1 +/- 0.7% in the newborn and 93.2 +/- 0.7% in the adult during NaHCO3 expansion (P less than 0.001). With either anion the higher fractional sodium reabsorption in the newborn was due to reabsorption of a greater fraction of the load presented to the distal nephron segment. The percent of the distal sodium load that was reabsorbed was 98.0 +/- 0.6% in the newborn and 92.2 +/- 1.0% in the adult during NaCl expansion, and 96.1 +/- 1.3% in the newborn and 81.5 +/- 2.4% in the adult during NaHCO3 expansion. Differences in distal nephron chloride, potassium and bicarbonate reabsorption among the groups support the hypothesis that the enhanced distal sodium reabsorption in the newborn occurred largely in the ascending loop of Henle with NaCl expansion, while it occurred in the late distal and cortical collecting tubules with NaHCO3 expansion. There was no difference between the natriuretic responses to NaCl or NaHCO3 in the newborn (P greater than 0.20); however, the natriuretic response to NaCl was less than that to NaHCO3 in the adult (P less than 0.001). This suggests that the bulk of the sodium that escaped reabsorption in Henle's loop during NaHCO3 expansion was reabsorbed in the late distal tubule in the newborn, but not in the adult.     

Mechanisms of release and renal tubular action of atrial natriuretic factor

Inasmuch as atrial natriuretic factor (ANF) is apparently involved causally in the renal response to acute hypervolemia, it became of interest to study cellular mechanisms of release and renal tubular action. To study release mechanisms, freshly excised rat heart atria were incubated in vitro. Activation of the cellular adenylate cyclase system by either beta-adrenergic stimulation or the vasopressin analog deamino-8-D-arginine vasopressin did not result in ANF release. By contrast, activation of the polyphosphoinositide system by alpha-adrenergic stimulation or stimulation of the V1-type vasopressin receptors, and by a calcium ionophore or active phorbol ester, significantly increased natriuretic activity in the medium and reduced it in tissue. It is concluded, therefore, that activation of this latter system is the mechanism for ANF secretion from atrial myocytes. To test the effect of ANF on tubular transport in the medullary collecting duct, microcatheterization was used in rats before and during i.v. infusion of synthetic atrial peptide (23 amino acids). It was found that tubular delivery of salt to this part of the nephron was increased, and that reabsorption in the duct itself was reduced. In control experiments, increased delivery was associated with proportionately increased reabsorption, which demonstrated glomerulotubular balance in the nephron segment under normal conditions. The natriuretic effect of ANF, therefore, was not caused solely by enhanced tubular load, but included specific inhibition of duct sodium reabsorption as an essential feature of the renal response.     

The glomerular filtration rate,effective renal plasma flow,and renal blood flow in the adult male chacma baboon (Papio ursinus)

Abstract: The radionuclide determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) has been validated in man, but not in the primate. GFR, ERPF, and renal blood flow (RBF) were measured in a group of 12 adult male chacma baboons using radiopharmaceuticals. GFR was determined using ^99mtechnetium-labelled diethylenetriamine-pentacetic acid. ERPF was measured with ¹³¹iodine-labelled hippuran. RBF, body surface area, and kidney weights were calculated using standard formulae. GFR was 49 ± 11 ml/min and ERPF was 237.9 ± 54.2 ml/min. Calculated RBF was 430.7 ± 111.9 ml/min and 507.4 ± 138.4 ml/min/100g of renal tissue. The results are in agreement with those obtained using more laborious nonradioisotopic techniques such as para-aminohippurate (PAH) and creatinine clearance and could serve as baseline normal values in the adult male chacma baboon.     

Micropuncture study of the renal responses of the urodele amphibian Necturus maculosus to injections of arginine vasotocin and an anti-aldosterone compound.

1. Necturus maculosus kidney function has been examined using standard clearance techniques and renal tubular micropuncture methodology. 2. Throughout, cyanocobalamin (vitamin B12) has been used to monitor glomerular filtration rate (GFR) and tubular water movements. It was established that this substance was handled by the Necturus kidney in a similar manner to inulin. It can be readily analysed, together with renal electrolytes, by electron microprobe techniques. 3. Profiles of transtubular gradients (TF:P ratios) along the nephron were established for osmolarity, sodium, potassium, calcium and cobalt (of cyanocobalamin). 4. Ureteral urine is always hyposmotic with respect to plasma and the site of dilution of the plasma ultrafiltrate is within the distal segment. 5. Up to 30% of the filtrate is isosmotically reabsorbed along the proximal tubule; the tubular fluid:plasma ratio for osmolarity and sodium is around 1, and the TF:P for cobalt of cyanocobalamin is about 1.4 by the end of this segment. 6. The renal effects of the neurohypophysial hormone arginine vasotocin (AVT) and an aldosterone antagonist (SC14266; Soldactone) have been examined. 7. AVT was consistently antidiuretic causing both a decreased GFR and an enhanced distal tubular reabsorption of water. 8. SC14266 also increased distal tubular reabsorption of water. Such an effect differs from that found in higher vertebrates, and may indicate a "glucocorticoid-type" of renal action for aldosterone in amphibians.     

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na⁺) or fell (low Na⁺). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

A study of nephron function in normal tropical residents using the creatinine and lithium clearances

 The kidney bears the brunt of the demands of a tropical climate for water and electrolyte homeostasis. We hypothesised that a tropical climate may cause adaptive changes in the entire organism leading to altered renal function in our subjects. Hence renal function data for residents of a temperate climate may not be applic- able to tropical residents. We therefore sought to elucidate renal function in subjects residing in a tropical climate. We used lithium clearance, C _Li, a non-invasive tool for assessing proximal tubular function in humans, and endogenous creatinine clearance, C _Cr, to estimate proximal tubular function and glomerular function, respectively, in our subjects. We did this in order to establish whether or not nephron function in our subjects differs from that for residents of a temperate climate. Nineteen male and 12 female Ghanaian subjects aged between 15 and 48 years were studied. The estimated G _Cr was 117.3±6.6 ml/min for male subjects and 97±6.4 ml/min for female subjects. C _Li was 20.3±1.6 ml/min for male and 19.1±0.4 ml/min for female subjects, respectively. The estimated absolute reabsorption rate of fluid of proximal tubules was 97.0±6.0 ml/min for males and 78.1±6.0 ml/min for females. The percentage proximal fluid reabsorption for male and female subjects was 81.2±1.4 and 79.5±1.6, respectively. The differences between male and female values (mean±SEM) were not statistically significant. The data suggest that the proximal tubule in residents of a tropical climate may reabsorb more fluid compared to that in residents of a temperate climate. Our values for proximal tubular reabsorption are higher than those reported for residents of a temperature climate. Our estimate of glomerular filtration, however, is similar to published data for Caucasians. The difference in proximal tubular function may reflect possible renal adaptation to a hot, humid climate. We conclude that renal function of tropical residents differs from that of residents of a temperate climate. This difference may be due to renal adaptation to the hot, tropical climate. Received: 1 July 1996 / Revised: 22 December 1996 / Accepted: 8 January 1997     

Losartan decreases glomerular filtration rate in isolated perfused porcine slaughterhouse kidneys

We investigated whether Losartan, an angiotensin II (Ang II) AT1 receptor antagonist, decreases renal vascular resistance (RVR) and increases glomerular filtration rate (GFR) in isolated perfused porcine slaughterhouse kidneys (11 control experiments and 11 Losartan experiments with 7.5mg Losartan in the preservation solution and 100(g/minute Losartan infused during perfusion). With perfusion, plasma renin activity (PRA) increased markedly from 3 +/- 1 to 90 +/- 17 ng Ang I/ml/h (control), and from 4 +/- 1 to 70 +/- 8 ng Ang I/ml/h (Losartan), plasma Ang II increased from 86 +/- 63 to 482 +/- 111 pg/ml (control), and from 73 +/- 42 to 410 +/- 91 pg/ml (Losartan). The GFR was decreased in Losartan experiments as compared with control experiments (5 +/- 1 versus 10 +/- 2 ml/min/100g kidney wt; p < 0.05). The RVR was the same in both groups (0.2 +/- 0.01 mm Hg/100g kidney wt/min/ml). Tubular sodium reabsorption was decreased in Losartan experiments as compared with control experiments (0.7 +/- 0.1 versus 1.4 +/- 0.3 mmol/min/100g kidney wt). Overall, Losartan accentuated pathophysiological signs of acute renal failure. Although other drugs have to be investigated, these results suggest that porcine slaughterhouse kidneys could be useful as a tool for research in areas such as transplantation and intensive-care medicine.