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PubMed1981

[Tryptophan metabolism in patients with vitiligo].

Our previous research showed that tryptophan is an important precursor in the biogenesis of melanins. Therefore, with the purpose of observing whether a relationship exists between tryptophan metabolism and diseases characterized by an altered process of skin pigmentation in man, we studied the metabolism of this aminoacid along the kynurenine pathway in 29 vitiliginous patients (11 males and 18 females) and in 21 control subjects (11 males and 10 females) by determining 10 urinary metabolites after an oral loading of 50 mg/kg body weight L-tryptophan. The mean total excretion of the metabolites in patients resulted similar to that of the controls. However, considering the individual metabolites one can observe a decreased excretion of 3-hydroxykynurenine, o-aminohippuric acid and 3-hydroxyanthranilic acid and an increased excretion of xanthurenic acid and of its 8-methyl ether in the group of vitiliginous patients in respect to the controls. These results seem to indicate a decreased formation of nicotinic acid from tryptophan. Moreover, in relation to the fact that 3-hydroxykynurenine could be the metabolite through which tryptophan is involved in melanin biosynthesis, this study supports the hypothesis of a connection of tryptophan metabolism with the lack of pigmentation in vitiligo.

3-Hydroxyanthranilic Acid↗

PubMed1992

Phosphate transport by capillaries of the blood-brain barrier.

Capillaries were isolated from bovine brain cortex and used for phosphate transport studies. The influx of phosphate through capillary membranes was studied by incubation with [32Pi]phosphate followed by a rapid filtration technique. Phosphate uptake by brain capillaries was mediated by a saturable high-affinity system which is independent of the sodium concentration in the incubation medium. The apparent half-saturation constant (Km) and maximal influx (Vmax) were estimated to 160 microM and 0.37 nmol/mg protein/30 s. Transport was inhibited by the phosphate analogues arsenate and phosphonoformic acid with apparent inhibition constants of 5 and 11 mM, respectively. The metabolic inhibitors cyanide and ouabain had no effect on the transport activity. Competition experiments showed that phosphate uptake was inhibited up to 41% by various anions (pyruvate, acetate, citrate, glutamate, and sulfate). In addition, phosphate uptake was significantly decreased by two selective inhibitors of anionic exchangers, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Chloride was not a substrate of the phosphate carrier as the replacement of external chloride, by nitrate, thiocyanate, or gluconate, did not increase phosphate transport. Aminohippuric acid and N'-methylnicotinamide, two specific substrates of anionic and cationic drug exchangers, did not compete with the phosphate carrier of cerebral capillaries. However, trans-stimulation with bicarbonate increased phosphate transport by 28%, and this stimulation was inhibited by 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, suggesting that the carrier of the cerebral capillaries could exchange phosphate with bicarbonate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMedDate not supplied

Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a new renin inhibitor). I: Single dose study.

This study describes the relationship between the measured effects (angiotensin I and renal plasma flow) and plasma drug levels using a combined pharmacokinetic-pharmacodynamic model after 90 min iv infusion of enalkiren in 15 healthy, salt-depleted subjects. Doses from 0.002 to 0.512 mg/kg were evaluated. One hour prior to enalkiren dosing, para-aminohippuric acid infusion was started for each subject and continued until 3 hr after the start of enalkiren infusion. Timed blood samples were obtained to measure enalkiren, para-aminohippuric acid, and angiotensin I levels in plasma. Enalkiren-induced effect changes lagged in time behind the plasma enalkiren level changes, showing a counterclockwise hysteresis loop. To relate the temporal relationship of effect changes accurately to plasma drug levels, a pharmacokinetic model was combined with a pharmacokinetic model that incorporated a hypothetical effect compartment. The magnitude of the time lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma enalkiren levels (t1/2keo). The t1/2keo for angiotensin I (0.002 hr) is significantly shorter than that of renal plasma flow (0.267 hr), indicating that enalkiren equilibrates more rapidly with the angiotensin I-related effect compartment than the renal plasma flow-related effect compartment. Moreover, the model allows for estimation of the effect site concentration that causes one-half of the maximal predicted effect (EC50), which is a measure of an individual's sensitivity to enalkiren. The EC50 of angiotensin I (81.1 ng/ml) is substantially lower than that of renal plasma flow (4414 ng/ml), indicating that angiotensin I may be a more sensitive measure of enalkiren effects than renal plasma flow.

Adult↗

PubMed1994

Functional characterization of the basolateral rat liver organic anion transporting polypeptide.

To characterize the transport functions of a recently cloned basolateral organic anion transporting polypeptide of rat hepatocytes we performed further kinetic transport and substrate cis-inhibition studies in organic anion-transporting polypeptide-cRNA injected Xenopus laevis oocytes. The studies demonstrate saturable Na(+)-independent sulfobromophthalein (Michaelis-Menten constant, 1.5 mumol/L) and taurocholate (Michaelis-Menten constant, 50 mumol/L) uptake by organic anion-transporting polypeptide. Sulfobromophthalein uptake was inhibited by the following organic anions: 0.01 mmol/L bilirubin (43%), 0.1 mmol/L indocyanine green (81%), 0.1 mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 52%) and 1 mmol/L probenecid (74%). Competitive inhibition was shown for indocyanine green (inhibition constant about 1.3 mumol/L). Sulfobromophthalein and taurocholate uptakes were also inhibited by cholate, chenodeoxycholate, deoxycholate and ursodeoxycholate, as well as their glycine and taurine conjugates. Organic anion-transporting polypeptide also mediated uptake of glycocholate, tauroursodeoxycholate and taurochenodeoxycholate. No cis-inhibition of sulfobromophthalein uptake was seen in the presence of ATP, para-aminohippuric acid, bumetanide, digitoxin, reduced glutathione, leukotriene C4, nicotinic acid, ouabain, oxalate, rifampicin, succinate or sulfate. Furthermore, radioactively labeled para-aminohippuric acid, alpha-ketoglutarate and reduced glutathione were not taken up by organic anion-transporting polypeptide in cRNA-injected frog oocytes. These data confirm that organic anion-transporting polypeptide represents a novel hepatocellular organic anion uptake system that can mediate Na(+)-independent transport of monovalent (e.g., bile acids) and divalent (e.g., sulfobromophthalein and indocyanine green) cholephilic organic anions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[Studies on the uptake of 8-anilino-1-naphthalene sulfonate by rat freshly isolated renal cells].

The addition of 8-anilino-1-naphthalene sulfonate (ANS) into rat renal cell suspension caused a rapid increase in fluorescence (Ex. 400 nm, Em. 470 nm). The increase in fluorescence seemed to be composed of two phases. When the cells were disrupted by ultrasonic wave, the fast phase (0-ca 20 sec) increased and the slow phase (after ca 40 sec) disappeared. The rate of increase in the slow phase was dependent on the concentration of ANS and on the ambient temperature. A double reciprocal plot of the rate and the concentration exhibited straight line. It was decreased by bromophenol blue and rose bengal but not by other organic anions like p-aminohippuric acid and several metabolic inhibitors. It seemed that the uptake of ANS into the renal cell is mediated by a carrier which is different from that for p-aminohippuric acid.

Anilino Naphthalenesulfonates↗

PubMed1998

Anti-diuresis in the blood-feeding insect Rhodnius prolixus Stål: antagonistic actions of cAMP and cGMP and the role of organic acid transport.

Secretion of primary urine by upper Malpighian tubules of the blood-sucking insect Rhodnius prolixus has recently been shown to be inhibited by cyclic GMP (cGMP). In the present work, we have demonstrated that cGMP has effects antagonistic to those of cAMP in Rhodnius tubules and have further characterized the effects of cGMP on tubular secretion. Cyclic GMP inhibited secretion at all concentrations from 5x10(-6) to 10(-3)M, though this inhibition was partially or wholly reversed by large (2mM) doses of cAMP. While sub-maximal concentrations of cGMP did not significantly alter [K(+)] and [Na(+)] of secreted fluid, high external [cGMP] reduced secretion to minimal levels and caused [K(+)] and [Na(+)] to approach pre-stimulation levels. Cyclic GMP does not appear to affect the permeability of the lower Malpighian tubule to water. Both cAMP and cGMP likely enter tubule cells by way of an organic acid transporter whose activity is induced by feeding. Sensitivity of the tubules to exogenous cGMP and cAMP, which is assumed to be a function of transport activity, reaches a peak approximately 5 days after the blood meal and declines rapidly thereafter. Transport of anions into upper tubules involves at least two different transporters: one for acylamides (e.g., p-aminohippuric acid) and another for sulphonates (e.g., amaranth, phenol red). Amaranth and phenol red blocked the actions of both cGMP and cAMP, whereas p-aminohippuric acid was without effect. This suggests that cyclic nucleotides enter by way of the sulphonate transporter.

Journal Article↗

PubMed1989

Study of postmortem blood circulation.

The objective of this work was to study the postmortem redistribution of blood volumes and its influence of the distribution of substances of different molecular weight (194.2 and 150,000 Da). Lipiodol Ultrafluide, Omnitrast, or a radioisotopic mixture of aminohippuric acid and human IgG were injected into the left ventricle of a total of 20 rabbits divided into three groups. Our results demonstrate the importance of related factors, including left ventricular postmortem contraction, the arterial vascular bed, diffusion processes connected to the physicochemical characteristics of the substances, and the anatomical distribution of the vessels. Postmortem diffusion of aminohippuric acid to the urine was observed.

Angiography↗

PubMed1986

Progressive glomerular sclerosis in experimental antiglomerular basement membrane glomerulonephritis.

A model of chronic progressive glomerular sclerosis in experimental antiglomerular basement membrane (anti-GBM) glomerulonephritis was developed in Wistar rats. Wistar rats given the accelerated form of anti-GBM anti-body glomerulonephritis initially developed significant proteinuria and renal insufficiency associated primarily with a decrease in glomerular filtration rate (GFR) with normal renal clearance of para-aminohippuric acid and with markedly reduced filtration fraction. The glomerular functional abnormalities were associated with marked glomerular hypercellularity due to leukocytic infiltration as well as proliferation of intrinsic glomerular cells with crescent formation. Late in the course of the disease, by day 21, GFR had fallen further, associated with a parallel decrease in the clearance of para-aminohippuric acid and a normal filtration fraction. At this stage, glomerular hypercellularity had diminished and was replaced by glomerular sclerosis. The model appears to be a reproducible form of chronic glomerulosclerosis and demonstrates that the chronic phase of glomerular basement membrane (GBM) glomerulonephritis is distinctly different from that of the acute phase. It provides a controllable setting to study the glomerular sclerotic process independent of the initial inflammatory changes.

Animals↗

PubMed2005

Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites.

It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogenous compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1. The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl derivative>7-methyl derivative>3-methyl derivative falling dotsxanthine>1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid>1,3-dimethyluric acid>1,7-dimethyluric acid>1-methyluric acid>uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds.

Animals↗

PubMed1997

A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in heart and lung transplant recipients.

BACKGROUND: Cyclosporine (CsA) is a potent immunosuppressive drug widely used in organ transplantation and in the treatment of autoimmune diseases (1, 2). However, its common nephrotoxic effect is a major limiting factor. Short-term CsA treatment has been shown to cause reversible renal vasoconstriction, whereas long-term treatment can lead to an afferent arteriolopathy and chronic renal failure. METHODS: We performed a randomized controlled trial to examine the short-term renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients. Sixteen patients each were randomized to receive a 6-week course of verapamil or control treatment (atenolol in hypertensive patients and placebo in normotensive patients) 1-2 months after transplantation. An 8-hr sequential clearance study of inulin and p-aminohippuric acid for estimating glomerular filtration rate and renal plasma flow, respectively, was performed at baseline and at completion of study. The integral area under the curve of the clearance parameter over 8 hr was then calculated to generate a clearance-time index. RESULTS: There was no difference in the clearance-time indices for inulin and p-aminohippuric acid between the two groups at baseline. However, at the completion of study, the within-group change in the glomerular filtration rate clearance-time index was different between the verapamil and control groups (48+/-20 vs. -35+/-17 ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal plasma flow, but did not reach statistical significance. Mean arterial blood pressure and whole-blood CsA levels did not differ between the two groups during the study. Verapamil treatment was also associated with a decrease in CsA dose requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at completion; P<0.001) without any significant change in trough whole blood CsA levels. Rejection episodes did not differ between the two groups. CONCLUSIONS: The use of verapamil in the heart or lung transplant recipients may therefore provide both renal protective effects and cost savings.

Adult↗

PubMed1987

The effect of fenoldopam, a dopaminergic agonist, on renal hemodynamics.

Fenoldopam, a dopaminergic agonist, was administered intravenously to 18 healthy male subjects in doses ranging from 0.025 to 1.0 microgram/kg/min for 2 hours. Three subjects were studied in a three-way crossover of fenoldopam at doses of 0.025, 0.10, and 0.50 microgram/kg/min. Fenoldopam decreased diastolic blood pressure and increased pulse rate without changing systolic blood pressure. Fenoldopam produced dose-related increases in para-aminohippuric acid clearance up to 75% at the 0.50 microgram/kg/min dose. This increase in renal blood flow was accompanied by increases in urine volume, water, and solute excretion; glomerular filtration rate was unchanged. Doses greater than 0.25 microgram/kg/min caused flushing and nasal congestion. The dopamine receptor antagonist metoclopramide (0.1 mg/kg/hr) did not block the systemic hemodynamic effects of fenoldopam but attenuated the increase in para-aminohippuric acid clearance. Fenoldopam plasma levels achieved steady state between 30 and 120 minutes after the start of the infusion and were linear with respect to infusion rate. Our findings show that intravenous fenoldopam causes systemic arteriolar vasodilation, accompanied by renal vasodilation and increased sodium excretion.

Adult↗

PubMed1981

Renal venous portal contribution to PAH and uric acid clearance in the chicken.

The contributions of the renal venous portal and the renal arterial circulations to the renal clearance of p-aminohippuric acid (PAH) and uric acid were determined in the unanesthetized chicken by the simultaneous use of the urinary clearance technique and the Sperber preparation. The [3H]PAH apparent tubular excretion fraction (ATEF) and the clearance of inulin (CIn) were used as indicators of the renal portal and renal arterial contributions, respectively, in a planar equation for total PAH clearance. This equation accurately reflects the renal clearance of PAH as well as the renal venous portal and renal arterial contributions to the total renal clearance of PAH. The equation suggests that under normal conditions approximately 50% of the renal clearance of PAH or uric acid comes from the renal venous portal circulation, with the remaining 50% coming from the arterial circulation. An inverse hyperbolic relationship between the filtration fraction (CIn/CPAH) and the [3H]PAH ATEF was found, demonstrating that the filtration fraction in the chicken decreases from a value of 18 to approximately 6% as the renal portal plasma flow increases from zero to a maximum value. Our equation for total clearance was also used with results of experiments on inhibition of uric acid excretory transport by L- and D-dopa and by probenecid to locate the probable sites of action of those inhibitors.

Aminohippuric Acids↗

PubMed1984

Tubular transport and metabolism of cimetidine in chicken kidneys.

Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion.

Animals↗

PubMed1978

Phlorizin stimulation of p-aminohippurate uptake in rat kidney cortex slices.

Phlorizin, 0.5 mM, increases the uptake of tritiated p-aminohippuric acid (PAH) in rat kidney cortex slices in vitro. Phlorizin also diminishes the rate of 3H-PAH washout from preloaded slices into PAH-free medium. At higher concentrations, phlorizin (5.0 mM) reduces slice uptake of 3H-PAH following short incubations but increases 3H-PAH accumulation after more prolonged incubations. Section freeze-dry autoradiography demonstrates that phlorizin inhibits secretion of 3H-PAH from cell to lumen in proximal tubules. Consequently, the increased 3H-PAH uptake and delayed washout induced by phlorizin may be attributed to effects at the antiluminal cell membrane. Phlorizin stimulation of PAH uptake occurs despite inhibition of secretion across the luminal membrane. Intracellular accumulation of 3H-phlorizin, demonstrable by autoradiography, provides direct evidence that cellular accumulation affords the glycoside access to both the luminal and antiluminal membrane in proximal tubules. These interactions between phlorizin and PAH suggest shared features of the membrane transport systems for secretion and reabsorption of sugars and organic acids in kidney.

Aminohippuric Acids↗

PubMed2002

Determinants of hypofiltration during acute renal allograft rejection.

This study sought to determine the extent to which GFR is decreased during acute renal allograft rejection in human subjects and to determine the mechanism of the decrease in GFR. Eight patients with biopsy-proven acute rejection were compared with 18 recipients of optimally functioning renal allografts. GFR and renal plasma flow (RPF) were measured as the clearance of inulin and para-aminohippuric acid, respectively. Arterial BP was determined, blood was sampled, and plasma oncotic pressure (pi(A)) was measured. Glomeruli obtained by biopsy during rejection were subjected to morphometric analysis, for determination of K(f). Control morphometric values for healthy glomeruli were provided by 10 living donors from whom biopsies were obtained at the time of organ donation. The subjects in the acute rejection group exhibited a significantly reduced GFR of 17 +/- 4 ml/min per 1.73 m(2), compared with 72 +/- 4 ml/min per 1.73 m(2) for control subjects (P < 0.001). With the use of a sensitivity analysis to take into account the unknown para-aminohippuric acid extraction ratio, the RPF rate was calculated to have likely been significantly decreased, by 45 to 70%, in the acute rejection group. Neither the plasma oncotic pressure nor the mean arterial pressure differed between the two groups. Morphometric analysis revealed no difference in the single-nephron K(f) values for the acute rejection group, compared with the control group. These results indicate that acute renal allograft rejection causes a profound decrease in GFR, which is attributable to a decrease in RPF alone or in combination with a decrease in the glomerular transcapillary hydraulic pressure gradient (DeltaP).

Acute Disease↗

PubMed1999

Unrecognized renal damage in critically ill patients.

INTRODUCTION: The objective of this study was to evaluate the percentage of unrecognized renal damage in patients with normal creatinine and urea in serum and normal creatinine clearance and to evaluate the usefulness of various proteins and enzymes as supplementary procedures for the investigation of renal function. MATERIAL AND METHODS: Forty critically ill male patients (APACHE II-score > 20, injury severity score > 15) were daily screened for a period of five days. In the 1st group there were 30 patients with normal creatinine and urea in serum and with normal creatinine clearances. In the second group there were ten patients with increased values of these parameters. The base-line condition of all patients and any changes in hemodynamic, nutrition and ventilation were noted. Clearances of inulin, para-aminohippuric acid, and creatinine were measured and the Cockcroft-Gault equation was calculated daily for a period of five days. Excretion of alpha-1-microglobulin. Tamm-Horsfall-protein, alanine aminopeptidase, angiotensinase A, albumin and immunoglobulin G were also measured daily. RESULTS: 21 Patients of group 1 and all patients of group 2 showed the expected correlation between the routine parameters of creatinine and urea in serum and the level of protein and enzyme excretion. Nine patients of group 1 (30%) showed normal glomerular filtration rates but pathological excretion fractions of all proteins and enzymes. CONCLUSIONS: Although all routine parameters of renal function (creatinine and urea in serum, creatinine clearance both by 24-h collection period and from the Cockcroft-Gault equation), and additionally inulin and para-aminohippuric acid clearance were measured, no references on tubular and glomerular damage were found in 30% of the investigated patients.

Acute Kidney Injury↗

PubMed1982

Riboflavin transport by rabbit kidney slices: characterization and relation to cyclic organic acid transport.

The transport of riboflavin and the relationship of riboflavin transport to the transport of the cyclic organic acids, aminohippurate and penicillin, were investigated in small renal slices in vitro. Riboflavin was accumulated by rabbit renal slices by a transport system that was inhibited by sugar-containing and sugarless flavins, cyclic organic acids including aminohippurate and penicillin, dinitrophenol and cold temperatures, but not by D-ribose or the weak base tolazoline. The transport of riboflavin into renal slices was not solely due to intracellular binding or metabolism of the riboflavin. Aminohippurate, penicillin and riboflavin inhibited the active accumulation of [14C] aminohippurate and [14C]penicillin by kidney slices. These studies support the notions that: 1) riboflavin is accumulated in kidney cortex slices by an energy-dependent saturable transport system; 2) riboflavin accumulation by kidney slices is inhibited by cyclic organic acids and sulfhydryl reagents, but not weak bases; and 3) riboflavin is a competitive inhibitor of aminohippurate as well as an inhibitor of penicillin G accumulation by kidney slices.

Aminohippuric Acids↗

PubMed1980

Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.

Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the vasodilator kinins, because the effect was not diminished by administration of either carboxypeptidase B (which destroys the kinins) or Trasylol (which blocks kinin synthesis). Thus, these results suggest that both angiotensin II, as well as metabolites of the PG-TX system, may be important determinants of postobstructive renal hemodynamics in the rat.

Angiotensin II↗