Preconditioning with sodium deficits to improve orthostatic tolerance in rats.

We hypothesized that prior deficits in total body sodium would improve the subsequent ability of non-hypovolemic rats to maintain arterial pressure when subjected to an orthostatic challenge. This hypothesis was based on similarities in the response of neurohumoral cardiovascular control systems to lower-body negative pressure and negative sodium balance. Sodium deficits were induced in male Sprague-Dawley rats for 7-8 d by feeding sodium restricted diets, or by administering furosemide daily. After this, rats were allowed to regain a positive sodium balance for 1 d by increasing dietary intake or withholding furosemide, and receiving additional normal saline intraperitoneally. Rats subjected to these protocols had equal plasma volumes at the time they were anesthetized and evaluated for orthostatic tolerance. Furosemide-treated rats maintained a higher mean arterial pressure (MAP) than controls (70 +/- 10 vs 34 +/- 9 mm Hg) when rotated to a 90 degrees head-up position for 20 s. Rats receiving the lowest dietary sodium maintained the highest MAP (89 +/- 8 mm Hg) when placed at 60 degrees head-up for 5 min. Both before and during the orthostatic challenges, prior furosemide treatment was associated with a higher peripheral resistance, while prior dietary restriction of sodium was associated with a higher cardiac output. We conclude that preconditioning consisting of chronic sodium deficits can improve orthostatic tolerance in this animal model. The hemodynamic data indicate the different modes of preconditioning may have their primary effect on different determinants of orthostatic tolerance.

Effects of ipsilateral denervation and contralateral ureteral obstruction on tubuloglomerular feedback.

The effects of acute ipsilateral denervation (AID) and contralateral ureteral obstruction on tubuloglomerular feedback (TGF) was studied by micropuncture in rats. Denervation alone was associated with an increase in the TGF turning point, the tubular flow rate required for a half-maximal TGF response, but other TGF characteristics were not affected. Contralateral ureteral obstruction alone was also associated with an increased turning point, but contralateral obstruction had no effect on turning point, when AID was done prior to the obstruction. We conclude that renal nerves have a tonic modulating effect on TGF in anesthetized rats, and that renorenal reflexes are involved in the TGF resetting associated with acute contralateral ureteral obstruction.

Captopril and tubuloglomerular feedback in remnant kidneys of prehypertensive rats.

The activity and characteristics of tubuloglomerular feedback (TGF) are altered subsequent to reductions in renal mass or blockade of the renin-angiotensin system. This study assessed the combined effects of renal ablation and captopril on TGF. Renal mass was reduced in male Sprague-Dawley rats by the surgical removal of 1 1/2 kidneys. At 2 and 8 wk postsurgery, TGF was studied by micropuncture before and after the administration of captopril (0.5 mg/kg i.v.) Before captopril, TGF in remnant kidneys (NX) was characterized by a higher tubular perfusion rate required for a 50% maximal response (TGF turning point) as compared with intact kidneys of controls (CNT) at both 2 (NX, 35 +/- 3; CNT, = 19 +/- 1 nL/min; P less than 0.05) and 8 wk (NX, 54 +/- 5; CNT, 20 +/- 1 nL/min; P less than 0.05). Captopril significantly increased the turning point in both intact and remnant kidneys at both 2 (NX, 43 +/- 2; CNT, 25 +/- 2 nL/min) and 8 wk (NX, 61 +/- 5; CNT, 28 +/- 2 nL/min) postsurgery. Captopril also significantly reduced the maximal TGF response in both intact and remnant kidneys at 2 (NX from 13 +/- 3 to 7 +/- 1 mm Hg; CNT from 10 +/- 1 to 5 +/- 1 mm Hg) and 8 wk (NX from 15 +/- 1 to 9 +/- 2 mm Hg; CNT from 13 +/- 1 to 7 +/- 1 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats.

Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 +/- 2 mmHg vs. 38 +/- 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 +/- 0.03 vs. 0.31 +/- 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 +/- 2 to 44 +/- 2 mmHg, P = 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 +/- 0.02-0.42 +/- 0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P = 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r = 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-dependent effects of chronic hypoxia on renin-angiotensin and urinary excretions.

The mechanisms regulating water, electrolyte, and blood volume homeostasis continue to mature in early postnatal life, and this maturation may be altered by perturbations of volume or cardiovascular status. To evaluate the long-term effects of chronic hypoxia on water balance, urinary electrolyte excretion, heart weights, systemic arterial pressure, and components of the renin-angiotensin system, male Sprague-Dawley rats were exposed to periods of simulated altitude of 10,000 ft up to 90 days of age beginning at 2 or 30 days of age. Altitude exposure of both neonatal and adult rats was associated with increases in urine output and water intake after 30 days of exposure, and right ventricular (RV) hypertrophy at all ages was examined. However, the percent increase in urine output, water intake, and RV hypertrophy was numerically greater in neonates. Neonates also had increases in urinary sodium and potassium excretion after 30 days of exposure. Plasma renin activity and serum angiotensin-converting enzyme (ACE) activity were not affected, but plasma renin substrate was reduced in both neonatal and adult altitude-exposed rats. Lung ACE activity was also decreased in altitude-exposed neonates. These data indicate that the degree and, in some cases, the nature of these homeostatic responses varies with age during long-term hypoxia.

Effects of dietary acidification and potassium depletion on acid-base balance, mineral metabolism and renal function in adult cats.

Effects of dietary potassium restriction, with or without dietary acidification, on acid-base balance, mineral metabolism and renal function were evaluated in 12 adult cats. Six cats were fed a potassium-restricted diet (0.2% potassium) for 8 wk, and six cats were fed the same potassium-restricted diet plus a dietary acidifier (0.8% NH4Cl) for 8 wk. Both groups of cats were then fed the same diet supplemented with potassium gluconate (0.7% dietary potassium) for an additional 4 wk. Renal function was evaluated before treatment and again at 8 and 12 wk. Serum potassium concentration declined in all cats by wk 1 and was also lower in NH4Cl-treated cats at 2, 3, 6 and 8 wk than in control cats. Metabolic acidosis developed in both groups of cats. Dietary balance studies indicated negative potassium balance in NH4Cl-treated cats. Glomerular filtration rate declined significantly in NH4Cl-treated cats after 8 wk but was unchanged in control cats. From the results of this study, we conclude that adding a dietary acidifier to a potassium-restricted diet worsens hypokalemia, possibly by affecting gastrointestinal potassium handling, and induces severe metabolic acidosis and renal dysfunction in adult cats.

Comparative effects of captopril and enalapril on the progression of chronic renal disease in partially nephrectomized rats.

Comparative effects of the angiotensin converting enzyme inhibitors captopril and enalapril on progression of chronic renal disease was studied in 3/4 nephrectomized rats. Rats were divided into sham and nephrectomized groups, and treated with plain water or water containing captopril (150 mg/liter) or enalapril (50 mg/liter). Evaluations were made 4 weeks before and 0, 4, 8, and 10 weeks after nephrectomy. Endogenous creatinine clearance decreased in drug-treated, nephrectomized rats to values less than sham controls, but remained greater than water-treated rats. Significant (P less than 0.05) proteinuria developed 4 weeks post-nephrectomy in water-treated rats, 8 weeks post-nephrectomy in captopril-treated rats, but did not develop in enalapril treated rats. Regression analysis of carbamylated plasma protein values vs plasma creatinine revealed significant (P less than 0.05) relationships only in the water-treated, nephrectomized rats from weeks 0 through 8, but were otherwise unaffected by treatment. Both drugs resulted in significantly (P less than 0.05) improved scores for renal histologic lesions as compared to water treatment. Modifications of proteinuria in captopril and enalapril-treated rats occurred prior to onset of changes in systolic blood pressure, which was significantly elevated only in water-treated, nephrectomized rats at weeks 8 and 10. We conclude that angiotensin converting enzyme inhibitors may ameliorate progression of experimental renal disease through intrarenal effects, independent of modulation of systemic blood pressure, and that enalapril may be superior to captopril in some regards.

Dose effect of captopril on renal hemodynamics and proteinuria in conscious, partially nephrectomized rats.

The effect of varying doses of captopril, an angiotensin I-converting enzyme inhibitor, on renal hemodynamics, systemic arterial pressure, and the progression of chronic renal disease in conscious, three-quarter nephrectomized adult male Sprague-Dawley rats was studied. Six weeks following nephrectomy (Week 0), rats were randomly divided into five groups. Group 2 (n = 8), 3 (n = 8), 4 (n = 9), and 5 (n = 5) were given 5, 10, 20, and 40 mg/kg captopril, respectively, daily in drinking water. Group 1 (n = 7) and sham-operated controls (n = 7) were given water only. On Weeks -6, 0, 2, and 4, renal function was assessed by 24-hr urinary protein excretion and plasma creatinine. Systolic blood pressure was measured at these times by the tail cuff method. Following Week 4, glomerular filtration rate and effective renal plasma flow were measured in conscious rats by single injection clearance of [3H]inulin and [14C]tetraethylammonium bromide, respectively. Group 1 had significantly higher (P less than 0.05) 24-h urinary protein excretion, plasma creatinine, and systolic pressure compared with Group 5 and controls by Week 4, whereas values for these parameters for Groups 2-4 ranged between these extremes. Although systolic pressures were not significantly different (P greater than 0.05), Group 2 had significantly lower proteinuria than Group 1 (P less than 0.05) at Week 4. Total kidney glomerular filtration rate was similarly decreased in Groups 1-5 compared with control rats. Total kidney effective renal plasma flow was higher in captopril-treated groups than in Group 1, whereas systolic blood pressure was similar or lower, indicating that captopril reduced renal vascular resistance. Furthermore, unlike Groups 1-3, the groups receiving higher doses of captopril (4 and 5) did not develop anemia associated with chronic renal disease. In conclusion, captopril attenuated renal functional deterioration in a dose-related manner. The effect on proteinuria was evident at low doses of captopril which did not significantly reduce systemic blood pressure and was accompanied by an increase in effective renal plasma flow and a decrease in renal vascular resistance.

Captopril or prostaglandin E1 ameliorate adverse renal hemodynamic effects of indomethacin in uninephrectomized rats.

Nonsteroidal anti-inflammatory drugs like indomethacin and angiotensin converting enzyme inhibitors like captopril have contrasting effects on compensatory changes in glomerular filtration rate and renal blood flow following partial nephrectomy. Conjoint treatment has been little studied. Effects of 7 days of treatment with captopril, indomethacin, or captopril + indomethacin in drinking water were studied in 50% nephrectomized Sprague-Dawley rats. Urinary protein excretion, glomerular filtration rate, effective renal plasma flow (ERPF), mean arterial pressure, renal vascular resistance, and remnant kidney weight were measured. Renal clearance studies were performed using a double-isotope, single-injection method, in conscious rats infused with either saline or saline + prostaglandin E1. Indomethacin induced significant (p less than 0.05) increases in renal vascular resistance (RVR) which were attenuated by either concurrent treatment with captopril or infusion of PGE1 at the time of study. Compensatory growth of the remnant kidney appeared not to be dependent on increments in renal blood flow; captopril decreased RVR and increased ERPF but had no effect on kidney weight, while indomethacin had no effect on ERPF and augmented remnant kidney weight. It appears effects of captopril and indomethacin on intrarenal hemodynamics in the residual kidney were counteractive, and that conjoint therapy in renal disease should be approached with caution.

Effect of clonidine on the progression of chronic renal disease in partially nephrectomized rats.

The effect of clonidine, on alpha 2-agonist and antihypertensive, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Treatments began four weeks after the removal of approximately 70% of renal mass. Clonidine was given once daily by gavage on an increasing dose schedule of 50 micrograms/kg for 4 weeks, followed by 100 micrograms/kg for 8 weeks and finally 200 micrograms/kg for 6 weeks. Measurements of renal functions were made at 4 week-intervals during treatment. After 18 weeks, clonidine-treated rats had lower levels of plasma urea nitrogen (P less than 0.05) and plasma creatinine (P less than 0.05). Urinary protein excretion rates were lower in clonidine-treated rats while receiving 100 micrograms/kg at 8 weeks (P less than 0.05) and 200 micrograms/kg at 18 weeks (P less than 0.05). At the end of the treatment period, anesthetized clonidine-treated rats had a numerically lower mean arterial pressure (p = 0.08), but no difference in the histological ranking of light microscopic lesions (P greater than 0.10). Based on the functional data, we conclude that clonidine retards the deterioration of renal function in this model of chronic renal disease. The lack of a consistent effect of clonidine on proteinuria and no reduction in the severity of morphological damage indicates that clonidine is less effective than previously reported treatment in this model with angiotensin converting enzyme inhibition. These differences in efficacy may be related to differences in intraglomerular hemodynamic alterations and could be an important consideration in the selection of therapies for individuals with hypertension and renal insufficiency.

Effect of propranolol on progression of chronic renal disease in partially nephrectomized rats.

The effect of propranolol, a beta adrenergic receptor blocking agent, on the progression of renal dysfunction in three-quarters nephrectomized adult male Sprague-Dawley rats was studied. Beginning four weeks after partial nephrectomy (week 0), rats received either 50 mg/kg propranolol (Group I) or distilled water (Group II) daily by gavage for 12 weeks. Renal function was measured by 24 hour urinary protein excretion, water intake, urine output, plasma creatinine, and plasma urea nitrogen at weeks -4, 0, 4, 8, and 12. Mean systolic blood pressure was measured by the tail cuff method. At the end of 12 weeks, rats were euthanatized, and remnant kidneys examined histologically. Group II rats were significantly (p less than 0.05) proteinuric compared to Group I rats at weeks 8 and 12. Mean systolic blood pressures of Group II rats were significantly greater (p less than 0.05) than group I rats on week 8. Both groups became significantly hypertensive (p less than 0.05) compared to week 0 values by week 12. Group II had significant (p less than 0.05) polyuria, polydipsia, and elevated plasma creatinine and urea nitrogen compared to Group I at week 12. Groups I and II could not be distinguished on the basis of renal histologic rank (p = 0.104). We conclude that propranolol attenuated the progression of chronic renal disease in this model.

Renal functional relationships in dogs with glomerulopathies.

Glomerular filtration rate, effective renal plasma flow, and filtration fraction were determined by measuring plasma disappearance of [14C] inulin and [3H]tetraethylammonium bromide after a single IV bolus injection was given to 8 dogs with membranous nephropathy, renal glomerulosclerosis, or renal amyloidosis. Glomerular filtration rate was decreased in the 8 dogs. Effective renal plasma flow was within reference values in 1 dog, increased in 1 dog, and decreased in 6 dogs. Filtration fraction was within reference values in 2 dogs and decreased in 6 dogs. The glomerular filtration rate also was estimated by the endogenous creatinine clearance technique and was decreased in the 8 dogs with glomerulopathies.

Effect of captopril on chronic puromycin aminonucleoside nephrosis in rats.

The effect of captopril, an angiotensin converting enzyme inhibitor, on the progression of chronic puromycin aminonucleoside (PAN) nephrosis was examined. Rats were injected with 15 mg/100 gm body weight PAN and 5 mg/100 gm body weight, on weeks - 1 and 5, respectively. A third group was injected with an equivalent volume of 0.9% saline, intraperitoneally (Group III) on week - 1 and 5. Beginning week 0, group I received 50 mg/kg captopril daily in the drinking water for 12 weeks. Group II received no treatment. Captopril failed to attenuate the peak level of proteinuria induced by the first injection of PAN or to alter the rate of decline of proteinuria when begun 1 week after the PAN injection. However, captopril did blunt the increase in urinary protein excretion following the second injection of PAN (p less than 0.05). Group II became hypertensive compared to Group I on week 8 and 12 and Group III on week 12 (p less than 0.05). Group I and II could not be distinguished on the basis of renal histologic rank (p = 0.80). We conclude that captopril affords some protection against the development of PAN-induced proteinuria, but it does not accelerate the recovery phase when glomerular permselectivity is being regained.

Single-injection method for evaluation of renal function with 3H-inulin and 14C-tetraethylammonium bromide in conscious unrestrained Sprague-Dawley rats.

A single-injection, double-isotope method for simultaneously determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in conscious, unrestrained rats was evaluated. 3H-inulin and 14C-tetraethylammonium bromide were used to determine GFR and ERPF, respectively. Using a modified, single exponential, 1-compartment, mathematical model, solute clearance was estimated, using a plasma radioactivity disappearance curve constructed from samples collected during a 60-minute period. In 12 healthy, conscious, adult male Sprague-Dawley rats, the mean (+/- SEM) GFR, ERPF, and filtration fraction were 5.65 +/- 0.40 ml/min/kg, 13.92 +/- 0.82 ml/min/kg, and 0.41 +/- 0.03, respectively. In 7 adult male Sprague-Dawley rats that had undergone a three-quarter nephrectomy 6 weeks prior to study, the mean GFR, ERPF, and filtration fraction were 2.69 +/- 0.36 ml/min/kg, 7.02 +/- 0.90 ml/min/kg, and 0.39 +/- 0.03, respectively. In 37 adult male rats in various stages of renal disease, the mean GFR and ERPF correlated significantly (r = 0.85, P less than 0.001 and r = 0.83, P less than 0.001, respectively) with the reciprocal of plasma creatinine. The single-injection, double-isotope technique yielded functional values similar to those reported for healthy rats in which other clearance methods were used. Using this technique, we were able to detect alterations associated with various degrees of renal functional loss. The technique enabled us to evaluate conscious, unrestrained rats, eliminated the need to collect urine, and required short blood collection times (60 min) and small volumes (0.1 ml) of plasma.

Renal resistance to mercuric chloride toxicity during prolonged exposure in rats.

An attempt was made to develop a model of chronic renal disease in the rat through repeated administration of a nephrotoxin specific for proximal tubular epithelium. Mercuric chloride was administered by subcutaneous injection in gradually increasing amounts over a period of 21 weeks. The dose ranged from 1.125 mg/kg once a week to 2.0 mg/kg twice a week. Measured parameters of renal function include plasma urea nitrogen, plasma creatinine, 24-hour urine output volume, and 24-hour urinary protein excretion. When compared to their own pretreatment values and those of the age/weight-matched control animals, the mercuric chloride-treated rats exhibited no significant abnormalities in these parameters of kidney function with the exception of a mild proteinuria at 21 weeks. Light microscopic examination of the kidneys of the mercury-treated rats revealed mild tubular, interstitial, and glomerular lesions which were significantly worse than those in the kidneys of the controls. This study demonstrates the ability of the kidney to sustain a considerable degree of resistance to inorganic mercury toxicity when exposure is continuous over a prolonged period of time. It also demonstrates the inability of commonly measured clinical laboratory parameters of kidney function to identify the effects of chronic mercuric chloride toxicity in the rat.

Effect of captopril on the progression of induced pyelonephritis in the rat.

The effect of captopril, an angiotensin-converting enzyme inhibitor, was studied in rats subjected to Escherichia coli pyelonephritis. Eight weeks after pyelonephritis was induced in male Sprague-Dawley rats, the rats were randomly assigned to treatment groups based on urinary protein excretion. In experiment 1, rats were given captopril, 50 mg/kg of body weight, or saline solution via daily intraperitoneal injection. To eliminate complications with captopril-induced peritonitis, experiment 2 was performed in which rats were given the same treatment by daily gavage. In both experiments, 24-hour urinary protein excretion in the saline-treated rats was significantly greater than that of the captopril-treated rats after 12 weeks of treatment (P less than 0.05). Plasma urea nitrogen, plasma creatinine, and endogenous creatinine clearance did not differ between treatment groups during the course of therapy in experiment 1. There were no differences in these values in experiment 2, except at week 8 of treatment when the captopril-treated rats had significantly lower plasma creatinine and higher endogenous creatinine clearance than did the saline-treated rats (P less than 0.05). There was also no difference between treatment groups in the degree of morphologic renal damage based on light microscopic evaluation of kidneys at the end of treatment.

The progression of adriamycin-induced nephrotic syndrome in rats and the effect of captopril.

The progression of adriamycin-induced nephrotic syndrome in rats was studied over a 3-month period. The effect of an angiotensin-converting enzyme inhibitor, captopril, on this model of renal disease, was also studied. Two weeks following a single iv injection of adriamycin, rats were divided into two treatment groups: one received a daily po dose of captopril and the other received a placebo. Measurements of renal function were performed at 4, 8, and 11 weeks following the initiation of therapy. Necropsies and light microscopic evaluation of the kidneys were performed at the end of the treatment period. Functional and morphologic alterations in both groups of rats were compared to each other and to normal age/weight-matched control rats studied over the same time period. At 13 weeks following the administration of adriamycin, both treatment groups had significant renal dysfunction when compared to normal controls. In addition to severe proteinuria, rats receiving adriamycin exhibited polyuria, polydipsia, increased plasma urea nitrogen and plasma creatinine, and decreased endogenous creatinine clearance. They had severe generalized kidney lesions characterized by tubular dilation and atrophy, cast formation, interstitial fibrosis and lymphocytic infiltration, and focal, global glomerulosclerosis. The histopathologic ranking of the kidneys was correlated with some antemortem laboratory parameters but not with the degree of proteinuria. Captopril had no ameliorating effects on the progression of renal disease. Certain findings indicate that captopril may actually have promoted the deterioration of renal function. We conclude that adriamycin-induced nephrotic syndrome in the rat is a progressive disease resulting in generalized renal dysfunction, and that captopril, at the dose given in this experiment, is unable to slow the progression of the disease.

Captopril slows the progression of chronic renal disease in partially nephrectomized rats.

The effect of captopril, an angiotensin-converting enzyme inhibitor, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Following ablation of approximately 70% of their renal mass, rats were divided into three treatment groups: group I received a placebo treatment; group II received daily po administrations of captopril; group III received captopril at the same dosage schedule as group II, but the drug was not given for 4 weeks in the middle of the treatment period. Measurements of renal function were performed at 4-week intervals, and light microscopic evaluation of the remnant kidneys was performed following 19 weeks of treatment. Deterioration of renal function, as measured by endogenous creatinine clearance, plasma creatinine, and plasma urea nitrogen, progressed more rapidly in group I than the other two groups. Twenty-four-hour urinary protein excretion was higher in group I than the others, except in group III following the 4-week period when captopril was not administered. Morphologic damage in the remnant kidney was significantly greater in group I than group II (p = 0.007). The renal lesions in the rats of group III were intermediate in severity. Histopathologic ranking of the remnant kidneys was correlated with antemortem laboratory parameters (r greater than or equal to 0.50; p less than 0.05). In a second experiment, similarly nephrectomized rats receiving po captopril daily had significantly longer survival, at 260 days, postnephrectomy than rats receiving a placebo (p = 0.0045). We conclude that captopril retards the progression of renal damage and increases survival time in this model of chronic renal disease. The mechanism may involve the alteration of potentially harmful intraglomerular hemodynamic changes which occur in the remnant kidney model.

Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats.

A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14C-inulin and ERPF was determined, using [3H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule.