P-aminohippuric Acid Clearance Research Articles

Acetaminophen nephrotoxicity in male Wistar rats.

Acute acetaminophen (APAP) nephrotoxicity was studied in male Wistar rats 1 h after different APAP single doses (200, 500 and 1000 mg/kg body wt, i.p.). Significant impairments in glomerular filtration rate (GFR) and clearance of p-aminohippuric acid (ClPAH) were observed in a dose-dependent way, although tubular parameters measured, water and electrolyte fractional excretion, remained at control values, while the urine to plasma osmolality ratios (Uosm/Posm) were diminished in APAP-1000 rats (control = 2.93 +/- 0.20, APAP-1000 = 1.40 +/- 0.04). The time course of renal function was also studied in APAP-1000 mg/kg-treated animals; parallel impairments were observed in GFR, ClPAH and tubular functions. Maximal alteration was observed at 16 h and restorement began at 24 h post-injection. Glucose renal handling, either at low or at high tubular glucose loads, remained at control values. Thus, our data suggest that the early stage of acetaminophen nephrotoxicity might be due to renal hemodynamic changes which might induce an alteration in tubular function principally in distal structures of medullary tissue, as shown by the Uosm/Posm results. These effects occurred coupled with a diminution in hepatic glutathione (GSH) levels at every APAP dose and in renal GSH levels in APAP-1000 mg/kg-treated rats. Moreover, renal damage was observed both in the presence or absence of hepatic damage.

Use of a thermal pulse decay system to assess avian renal blood flow during reduced renal arterial perfusion pressure

Using a simplified avian kidney model, renal arterial perfusion pressure (RAPP) was reduced from 120 (control) to 70 mmHg (near the glomerular filtration rate autoregulatory limit) and then to 46 mmHg (below the glomerular filtration rate autoregulatory range) in kidneys with ambient or partially restricted renal portal flow. Renal blood flow (RBF) was measured with a thermal pulse decay (TPD) system, using TPD thermistor probes inserted at three locations to evaluate regional differences in RBF. The clearance (CPAH) and extraction of p-aminohippuric acid were used to calculate renal plasma flow (RPF). CPAH, RPF, and RBF values were consistently lower for kidneys with restricted portal flow than for kidneys with ambient portal flow. Reducing RAPP to 46 mmHg did not significantly reduce CPAH, RPF, or RBF in the ambient group but did significantly reduce CPAH and RPF (regressed on RAPP) in the restricted group. RBF was not significantly affected when RAPP was reduced in the restricted group, although significant regional differences in blood flow were recorded. Renal vascular resistance decreased significantly as RAPP was reduced to 46 mmHg in the ambient group, confirming the renal autoregulatory response. In separate validation studies, significant reductions in RBF were detected by the TPD system during acute obstructions of portal and/or arterial flow. Overall, the results support previous evidence that avian RBF remains constant over a wide range of RAPPs. Observations of nonuniform intrarenal distributions of portal blood flow suggest that the portal system maintains the constancy of RBF in regions with proportionately high portal-to-arterial flow ratios.

Long-Term Antihypertensive and Renal Effects of Isradipine in Hypertensive Patients with Normal and Reduced Renal Function

The long-term hemodynamic and antihypertensive effects of isradipine were investigated in 11 patients who had normal renal function and 9 who had reduced renal function. The dose regimen was 1.25–5 mg twice daily, depending on blood pressure response. After 24 weeks of active treatment, systolic/diastolic blood pressure decreased from 172/106 to 155/94 mm Hg (p < 0.05) in the patients with normal renal function, and from 176/105 to 169/93 mm Hg (p < 0.01) in those with impaired renal function. Contrary to the results of short-term treatment, no changes in inulin and p-aminohippuric acid (PAH) clearances were observed in either study group. There were no significant changes in plasma renin, aldosterone, glucose, or lipids, nor were there changes in protein excretion in either group; however, sodium excretion increased significantly in both groups. On the basis of our results, we conclude that isradipine has a place in the treatment of hypertensive patients with mild renal insufficiency.

Long-Term Antihypertensive and Renal Effects of Isradipine in Hypertensive Patients with Normal and Reduced Renal Function

The long-term hemodynamic and antihypertensive effects of isradipine were investigated in 11 patients who had normal renal function and 9 who had reduced renal function. The dose regimen was 1.25-5 mg twice daily, depending on blood pressure response. After 24 weeks of active treatment, systolic/diastolic blood pressure decreased from 172/106 to 155/94 mm Hg (p less than 0.05) in the patients with normal renal function, and from 176/105 to 169/93 mm Hg (p less than 0.01) in those with impaired renal function. Contrary to the results of short-term treatment, no changes in inulin and p-aminohippuric acid (PAH) clearances were observed in either study group. There were no significant changes in plasma renin, aldosterone, glucose, or lipids, nor were these changes in protein excretion in either group; however, sodium excretion increased significantly in both groups. On the basis of our results, we conclude that isradipine has a place in the treatment of hypertensive patients with mild renal insufficiency.

Spontaneously hypertensive rats demonstrate increased renal vascular alpha 1-adrenergic receptor responsiveness

To determine alpha 1-adrenergic receptor responsiveness of the renal vasculature in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), phenylephrine (2.5 or 5.0 micrograms.kg-1.min-1 iv) or saline was infused. Effective renal blood flow (ERBF) and glomerular filtration rate were determined by p-aminohippuric acid and inulin clearances, respectively. Peritubular capillary, proximal tubular, and stop-flow pressures (SFP) were measured by micropuncture. Phenylephrine decreased ERBF (6.27 +/- 0.48 to 4.55 +/- 0.65 ml.min-1.g-1; P less than 0.05) and increased arterial pressure and SFP (31.5 +/- 0.9 to 34.2 +/- 1.0 mmHg) in SHR. It only increased arterial pressure and ERBF in WKY without changing SFP. Afferent arteriolar resistance (RA) and glomerular capillary pressure (PG) remained unchanged, whereas efferent resistance (RE) decreased in WKY; in contrast, RA, RE, and PG increased in SHR (RA 21.2 +/- 2.0 to 38.1 +/- 7.1 mmHg.ml-1.min.g, RE 6.9 +/- 0.6 to 13.9 +/- 3.8 mmHg.ml-1.min.g; and PG 49.6 +/- 0.9 to 53.7 +/- 1.1 mmHg; all P less than 0.05). These data demonstrated increased SHR afferent and efferent arteriolar responsiveness; WKY efferent arteriolar hyperresponsiveness was not observed. The findings support the concept of augmented intrarenal vascular alpha 1-adrenergic responsiveness in hypertension that may predispose to subsequent glomerular hypertension.

Prediction of the renal clearance of cimetidine using endogenousN-1-methylnicotinamide

We investigated the influence of the type rather than the degree of renal insufficiency on the renal clearance of drugs. Different models of site specific experimental renal failure (ERF) have been developed in the rat; proximal tubular necrosis, induced by cisplatin; papillary necrosis, induced by 2-bromoethylamine, and glomerulonephritis, induced by sodium aurothiomalate or by antiglomerular basement membrane antibody. Several parameters of kidney function were assessed: the clearance of inulin, PAH, and endogenous N-1-methylnicotinamide (NMN). Plasma BUN and creatinine concentrations, and the presence of proteinuria and glucosuria were also measured. Our results showed a nonparallel decrease in glomerular filtration rate (GFR) and tubular secretion as measured by the secretory clearance of endogenous NMN or by the secretory clearance of p-aminohippuric acid (PAH), that is incompatible with the "intact nephron hypothesis." As a result, the renal clearance of cimetidine, a drug eliminated mainly by renal secretion, correlated better with the renal clearance of endogenous NMN than with the GFR. We conclude that (i) our models of ERF demonstrated the existence of glomerulo-tubular imbalance that is contrary to expectations based on the intact nephron hypothesis; (ii) the type of the renal disease has a direct influence on the renal clearance of cimetidine; (iii) the clearance of endogenous NMN may be a valuable noninvasive test for assessing renal tubular secretion which could be useful in predicting the clearance of drugs eliminated predominantly by tubular secretion.

Flow-dependent extraction of 1-naphthol by the rat isolated perfused kidney

The influence of variation of perfusion flow rate on the renal clearance of p-aminohippuric acid and 1-naphthol was studied with an isolated perfused rat kidney preparation. Kidney functions were well maintained at low perfusion flow rates by the use of a fluorocarbon emulsion to increase the oxygen capacity of the perfusion buffer. Renal extraction of p-aminohippuric acid decreased with increasing perfusion flow. Our data show that at high perfusion flow rates maximal extractable perfusion flow forms only a small part of the total perfusion flow. 1-Naphthol is rapidly metabolized to its glucuronide and sulfate conjugate in the isolated perfused rat kidney. Using PAH as a marker for the maximal extractable perfusion flow, 1-naphthol could be regarded as a high-extraction compound even at high perfusion flow rates. Our results suggest that p-aminohippuric acid clearance, rather than total perfusion flow rate, should be used as the measure of maximal extractable blood flow for the estimation of extraction ratio in the isolated perfused kidney of compounds excreted or metabolized by the proximal tubules.

Renal and humoral responses to sustained cardiopulmonary baroreceptor deactivation in humans

The renal and neurohumoral effects of prolonged cardiopulmonary baroreflex unloading and the relationship of these changes to urinary sodium excretion have not been well documented in humans. In this study, 12 normal males underwent lower body negative pressure at -15 mmHg for 90 min, a maneuver that deactivates cardiopulmonary baroreceptors. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF) were measured in eight of these subjects using inulin and p-aminohippuric acid clearance techniques. During reduction of central venous pressure, arterial blood pressure and heart rate did not change. Plasma concentrations of atrial natriuretic factor (ANF) decreased markedly (22 +/- 2 to 12 +/- 1 pg/ml, P = 0.0001) as did the second messenger of ANF's biological action, guanosine 3',5'-cyclic monophosphate, whereas renin and vasopressin were not significantly altered. There was a significant rise in plasma norepinephrine (1.6 +/- 0.2 to 2.4 +/- 0.4 nmol/l, P = 0.03). GFR (104 +/- 9 to 68 +/- 6 ml/min, P = 0.007) and FF (0.18 +/- 0.01 to 0.14 +/- 0.01, P = 0.007) decreased significantly, with maintenance of ERPF. There was a significant antinatriuresis without an antikaliuresis and a significant reduction in free water clearance. These changes in renal hemodynamics are unlike the known effects of renal vasoconstrictors, and the alterations in solute and free water clearance are consistent with the removal of the known actions of ANF from tubular target sites. Taken together, our findings suggest that a mechanism other than activation of vasoconstrictors, possibly the diminution of the influence of ANF on the kidney, may be operative in the renal adjustments to cardiopulmonary baroreflex deactivation in humans.

Hyperoxemia Does Not Affect Renal Hemodynamics and Function in Newborn Rabbits

Renal hemodynamics and function were assessed in 10 anesthetized newborn rabbits undergoing acute hyperoxemia for 1 h. The hyperoxemic period either followed (group 1: n = 5) or preceded (group 2: n = 5) a normoxemic control period. Renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by the clearance of p-aminohippuric acid and inulin, respectively. Urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction and sodium fractional excretion remained unchanged throughout the study whatever the order of the normoxemic and hyperoxemic periods. It is concluded that hyperoxemia up to PaO2 of 170 mm Hg does not alter renal function.

Platelet-Activating Factor Mediates Glycerol-Induced Acute Renal Failure in Rats

1. We have studied the effect of inhibiting the interaction of platelet-activating factor with its receptor by using two structurally different antagonists BN-52021 (1 mg/kg, intraperitoneally) and alprazolam (1 and 5 mg/kg, intraperitoneally) on the evolution of glomerular filtration and renal blood flow, in the experimental model of acute renal failure induced by the intramuscular injection of glycerol in rats. 2. We have also measured arteriovenous differences in platelet-activating factor concentration, as well as platelet-activating factor content in glomeruli from rats with glycerol-induced acute renal failure. 3. After glycerol injection, untreated rats showed a marked reduction in inulin clearance which reached 77% in the first 30 min. The reduction was only 27% in the rats treated with BN-52021 and 38% in the rats treated with alprazolam (5 mg/kg), with statistically significant differences between treated and untreated groups. 4. Clearance of p-aminohippuric acid was also improved with BN-52021 or alprazolam treatment. 5. This protective effect of BN-52021 was observed in a more prolonged follow-up (3 days). 6. Glomeruli from rats with acute renal failure, treated or untreated with BN-52021, showed similar amounts of platelet-activating factor, whereas it was undetectable in glomeruli from normal rats. Furthermore, rats with glycerol-induced acute renal failure released greater amounts of platelet-activating factor. 7. These results provide evidence of a role for platelet-activating factor in the genesis of this model of experimental acute renal failure.

Influence of hydration on ultrafilterable platinum kinetics and kidney function in patients treated withcis-diamminedichloroplatinum(II)

It has been reported that hypertonic saline provides protection against the renal toxicity of cisplatin (CDDP). We therefore evaluated its influence on the plasma and urinary pharmacokinetics of ultrafilterable platinum and kidney function as estimated by creatinine, inulin and PAH clearance. We undertook a randomized trial including two groups of ten patients receiving 100 mg/m2 CDDP in isotonic (group 1) or hypertonic saline (group 2) by a 20-min infusion. The hydration consisted of dextrose in group 1 and isotonic saline in group 2. Maximal concentration (Cmax), protein binding and cumulative urinary excretion were significantly higher in the dextrose group. Urinary flow decreased in this group but not in the other one. Inulin clearance was higher in the dextrose group than in the saline group and P-aminohippuric acid (PAH) clearance was not significantly different in these groups of patients. Hyponatremia was observed in the dextrose group. These results suggest that hypertonic saline infusion and saline hydration may enhance the diffusion of CDDP into tissues, lowering Cmax and renal excretion of platinum. The reduction of protein binding may indicate a diminution of aquation of CDDP in plasma. Our results suggest that the infusion of CDDP in hypertonic saline with salt hydration could exert a protective effect on the kidney. Moreover, there is a lessening of the risk of cellular hyperhydration. However, the better influence of dextrose hydration on glomerular filtration leads us to recommend a combination of the two methods of hydration for better tolerance and efficacy.

Renal and systemic hemodynamic responses to sustained submaximal exertion in horses

We investigated the effects of 1 h of sustained submaximal exertion on the renal and systemic hemodynamics of six horses. The horses ran on a treadmill at a speed that produced heart rates of 55-60% of each horse's maximum heart rate. Exertion produced heart rates of 121 +/- 6.6 and 126 +/- 6.1 (SE) beats/min after 15 and 60 min, respectively. Cardiac output increased significantly (P less than 0.05) from 70.1 +/- 3.1 to 246.2 +/- 4.7 ml.min-1.kg body wt-1 after 15 min of exertion and thereafter did not change. There was no significant change from rest in p-aminohippuric acid and creatinine clearances, filtration fraction, or renal blood flow during exertion. Plasma total solid concentration and hematocrit increased by 3.8 and 8.6%, respectively, between 20 and 60 min of exertion. Pulmonary artery temperature increased significantly from 37.6 degrees C at rest to 38.6 degrees C at 60 min of exertion. This study demonstrates the ability of the horse to maintain renal hemodynamics similar to resting values and systemic hemodynamics at steady-state values despite hemoconcentration and increased body temperature during sustained submaximal exertion.

Effect of furegrelate on renal plasma flow after angiotensin II infusion

We had previously shown that selective thromboxane synthetase inhibition with furegrelate increases urinary excretion of 6-ketoPGF1 alpha, the hydrolysis product of prostacyclin after stimulation of renal prostaglandin synthesis with furosemide. The present study assessed the functional significance of this "redirection" of prostaglandin formation using a more physiologic stimulus, angiotensin II. Sprague-Dawley rats (n = 27) were fitted with a transabdominal bladder cannula. Five days later they were given angiotensin II (10 mg.kg-1.min-1) by intravenous infusion. After 30 min, an infusion of furegrelate, 2 mg/kg, then 2 mg.kg-1.h-1, (n = 9); indomethacin, 2 mg/kg, then 2 mg.kg-1.h-1 (n = 9); or vehicle, 250 microL, then 0.018 mL/min (n = 9) was begun for 60 min. Clearance of [14C]para-aminohippuric acid was taken as a measure of renal plasma flow. Angiotensin II raised the mean arterial pressure in all groups. Administration of furegrelate or indomethacin did not change mean arterial pressure or heart rate. Angiotensin II reduced [14C]p-aminohippuric acid clearance by about 32% (1.42 +/- 0.18 to 0.97 +/- 0.07 mL.min-1.100 g-1, p less than 0.05). Furegrelate attenuated this renal vasoconstriction (0.97 +/- 0.07 to 1.38 +/- 0.17 mL.min-1.100 g-1, p less than 0.05), while indomethacin increased it by a further 32% (1.78 +/- 0.12 to 1.20 +/- 0.12 mL.min-1.100 g-1, p less than 0.05). Vehicle alone had no effect. Furegrelate reduced serum thromboxane B2 by 90% (6.52 +/- 0.030 to 0.7 +/- 0.21 ng/100 microL, p less than 0.05), while indomethacin reduced it by 73% (5.9 +/- 0.99 to 1.4 +/- 0.20 ng/100 microL, p less than 0.05). We conclude that furegrelate attenuates the renal vasoconstriction of angiotensin II, presumably by enhancing the formation of vasodilator prostaglandins.

Direct effects of endothelin in the rat kidney

In the present study, we tested the direct effects of endothelin (ET) on rat kidney in vivo. ET was infused into the left renal artery of anesthetized rats at a rate of 0.5, 5, 20, or 40 pmol/h. ET reduced ipsilateral urine volume (V), clearance of inulin (CIN), and clearance of p-aminohippuric acid (CPAH) in a dose-dependent manner. Thus ET at 20 pmol/h did not change V but decreased renal plasma flow (RPF) and glomerular filtration rate (GFR) by 27.6 +/- 14.3 and 30.8 +/- 10.4%, respectively, in the ipsilateral kidney. ET at 0.5 pmol/h was without effect and at 5 pmol/h had only minor effects on CIN and CPAH of ipsilateral kidney. At 40 pmol/h, ET reduced ipsilateral V, GFR, and RPF by 52.3 +/- 21.4, 58.4 +/- 14.5, and 72.5 +/- 10.6%, respectively. Filtration fraction and fractional excretion of Na remained unchanged during ET infusion. ET, 40 pmol/h, infused into the renal artery together with atrial natriuretic peptide (ANP) at a rate of 12 pmol/h reduced the ipsilateral V, GFR, and RPF by 33.2 +/- 6.3, 26.1 +/- 6.0, and 27.2 +/- 7.1%, respectively, decrements less than those with ET alone. When a calcium-channel blocker nicardipine was infused at a rate of 2.5 micrograms/h into the renal artery together with ET, 20 pmol/h, there was little change in the ipsilateral V, RPF, and GFR; ET, 40 pmol/h, with nicardipine did not change V and decreased GFR and RPF by 25.9 +/- 5.6 and 23.1 +/- 10.8%, respectively, decrements less than those without nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline

Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.

Age dependence of renal function: clearance of iohexol and P-amino hippurate in healthy males

Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.

Natriuretic Response to Volume Expansion in Polycystic Kidney Disease

Hypertension is an early manifestation of autosomal dominant polycystic kidney disease (ADPKD). Whether polycystic kidneys have an intrinsic abnormality that leads to sodium retention, volume expansion, and hypertension is uncertain. We studied the natriuretic response to a 4-hour infusion of physiologic saline at a rate of 6.5 ml/kg per hour in 10 patients with ADPKD who had normal renal function and 10 gender- and age-matched control subjects. Baseline 24-hour urinary excretions of sodium and potassium were similar in both groups. The baseline filtration fraction was significantly higher in the patients with ADPKD than in the control subjects. During the infusion of saline, no significant changes in blood pressure, clearance of inulin, or clearance of p-aminohippuric acid were detected. The increase in fractional excretion of sodium over baseline was significantly higher in the patients with ADPKD than in the control subjects. The pressure-natriuresis regression line was significantly shifted to the right in patients with ADPKD who had hypertension. The fractional excretion of potassium was significantly lower in patients with ADPKD than in control subjects. No significant differences in plasma renin activity, aldosterone, or atrial natriuretic factor were detected between the two groups. These observations suggest the presence of subtle abnormalities in the management of renal sodium that might contribute to the development and maintenance of hypertension in patients with ADPKD.

Differential effects of the degree of renal damage on p-aminohippuric acid and inulin clearances in rats.

Kidney disease is generally thought to affect all segments of a nephron equally. Bricker and co-workers first proposed this as the Intact Nephron hypothesis in 1971, and evidence to date has usually supported this hypothesis. However, most supporting studies have involved severe renal failure, which may not be suitable to differentiate effects on functional sites or to test the hypothesis. The work included here examines the effects of limited renal failure on two separate functions of the nephron: glomerular filtration, as measured by inulin clearance and proximal tubular organic anion secretory function, as measured by p-aminohippuric acid (PAH) clearance. Renal failure was induced in rats by intravenous administration of uranyl nitrate, a nephrotoxin. Doses used were 0.3, 1.0, and 3.0 mg/kg rat body weight. Five days later, rats were given an intravenous infusion of PAH and inulin. Renal clearance of each compound was calculated. Results obtained in these experiments show that, at the lowest uranyl nitrate dose, PAH clearance was significantly decreased but inulin clearance was not. The ratio of CLPAH/CLIN was decreased from 2.55 in control rats to 1.21 in rats given the low dose of nephrotoxin. At higher uranyl nitrate doses, both clearance rates were significantly decreased and the ratio of CLPAH/CLIN remained close to 1.0. These results indicate that the active transport functions of the nephron can be differentiated from passive transport functions. Caution should be exercised in extrapolating renal disease changes in active renal secretion to changes in passive renal elimination and the reverse.

Response to atrial natriuretic peptide in dogs with hypovolemic acute pancreatitis

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.

Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males.

Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.