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H Osswald

Publications and source records attributed to H Osswald.

At least 19 recordsLinked to original sources
PubMed2001

The selective adenosine A1 receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency.

Several studies have recently suggested a principal role of adenosine in the pathogenesis of radiocontrast media-induced nephropathy. In the present experiments, we therefore investigated the renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective adenosine A1 receptor antagonist, on radiocontrast media-induced nephropathy in the model of the N-pi-nitro-L-arginine methyl ester (L-NAME) hypertensive, chronic nitric oxide (NO)-depleted rat. Chronic NO depletion was induced by pretreatment with L-NAME, 50 mg/ml, added to drinking water for 8 weeks. Clearance experiments were performed in anesthetized rats and glomerular filtration rate was assessed prior to and following the application of high osmolar radiocontrast media (sodium diatrizoate, 3 ml/kg, i.v.) or an equivalent volume of isoosmolar mannitol to examine the role of hyperosmolarity in radiocontrast media-induced nephropathy. Subgroups received KW-3902 (0.1 mg/kg, i.v.), 20 min prior to radiocontrast media administration. Age-matched, untreated rats served as controls. Radiocontrast media application induced a significant decline in glomerular filtration rate in L-NAME hypertensive animals, whereas no effects were observed in control rats. KW-3902 fully prevented the drop in glomerular filtration rate in response to radiocontrast media in L-NAME hypertensive rats. No renal hemodynamic alterations were observed in mannitol-infused animals. The present experiments demonstrate that the decrease in glomerular filtration rate following radiocontrast media occurred independently of the osmotic load, and that KW-3902 effectively prevented the radiocontrast media-induced deterioration in renal function. KW-3902 may be especially beneficial in patients at high risk for developing acute renal failure following radiocontrast media application or in patients in which extracellular fluid volume expansion is limited by clinical conditions such as congestive heart failure.

Animals↗
PubMed2000

Sodium reabsorption in thick ascending limb of Henle's loop: effect of potassium channel blockade in vivo.

1. Based on previous in vitro studies, inhibition of K(+) recycling in thick ascending limb (TAL) is expected to lower Na(+) reabsorption through (i) reducing the luminal availability of K(+) to reload the Na(+)-2Cl(-)-K(+) cotransporter and (ii) diminishing the lumen positive transepithelial potential difference which drives paracellular cation transport. 2. This issue was investigated in anaesthetized rats employing microperfusion of Henle's loop downstream from late proximal tubular site with K(+)-free artificial tubular fluid in nephrons with superficial glomeruli. 3. The unselective K(+) channel blocker Cs(+) (5 - 40 mM) dose-dependently increased early distal tubular delivery of fluid and Na(+) with a maximum increase of approximately 20 and 185%, respectively, indicating predominant effects on water-impermeable TAL. 4. The modest inhibition of Na(+) reabsorption in response to the 15 mM of Cs(+) but not the enhanced inhibition by 20 mM Cs(+) was prevented by luminal K(+) supplementation. Furthermore, pretreatment with 20 mM Cs(+) did not attenuate the inhibitory effect of furosemide (100 microM) on Na(+)-2Cl(-)-K(+) cotransport. 5. Neither inhibitors of large (charybdotoxin 1 microM) nor low (glibenclamide 250 microM; U37883A 100 microM) conductance K(+) channels altered loop of Henle fluid or Na(+) reabsorption. 6. The intermediate conductance K(+) channel blockers verapamil and quinine (100 microM) modestly increased early distal tubular Na(+) but not fluid delivery, indicating a role for this K(+) channel in Na(+) reabsorption in TAL. As observed for equieffective concentrations of Cs(+) (15 mM), Na(+) reabsorption was preserved by K(+) supplementation. 7. The results indicate that modest inhibition of K(+) channels lowers the luminal availability of K(+) and thus transcellular Na(+) reabsorption in TAL. More complete inhibition lowers paracellular Na(+) transport probably by reducing or even abolishing the lumen positive transepithelial potential difference. Under the latter conditions, transcellular Na(+) transport may be restored by paracellular K(+) backleak.

Adamantane↗
PubMed2000

Postglomerular vasoconstriction induced by dopamine D(3) receptor activation in anesthetized rats.

In the present study we investigated the renal hemodynamic effects of dopamine D(3) receptor activation by R(+)-7-hydroxy-dipropylaminotetraline (7-OH-DPAT) in thiopental-anesthetized Sprague-Dawley rats. In clearance experiments infusion of 7-OH-DPAT (0.01-1.0 microg. kg(-1). min(-1)) dose-dependently elevated glomerular filtration rate (GFR) without affecting mean arterial blood pressure (MAP). In renal blood flow experiments 7-OH-DPAT infusion (1.0 microg. kg(-1). min(-1)) increased GFR by 16 +/- 2%, associated with an unexpected fall in renal blood flow by 20 +/- 3% and a significant elevation of renal vascular resistance by 18 +/- 3%. The renal hemodynamic changes were not influenced by pretreatment with the D(2)-receptor antagonist S(-)-sulpiride but were completely abolished during D(3) receptor inhibition by 5,6-dimethoxy-2-(di-n-propylamino)indane (U-99194A). In micropuncture experiments 7-OH-DPAT (1.0 microg. kg(-1). min(-1)) significantly elevated stop-flow pressure measured in the early proximal tubules and reduced hydrostatic pressure at the first branching point of the efferent arteriole without altering MAP. We conclude from these data that pharmacological activation of dopamine D(3) receptors affects renal hemodynamics in anesthetized rats by preferential postglomerular vasoconstriction.

Animals↗
PubMed2000

Localization of S-adenosylhomocysteine hydrolase in the rat kidney.

S-adenosylhomocysteine (SAH) hydrolase is a cytosolic enzyme present in the kidney. Enzyme activities of SAH hydrolase were measured in the kidney in isolated glomeruli and tubules. SAH hydrolase activity was 0.62 +/- 0.02 mU/mg in the kidney, 0.32 +/- 0.03 mU/mg in the glomeruli, and 0.50 +/- 0.02 mU/mg in isolated tubules. Using immunohistochemical methods, we describe the localization of the enzyme SAH hydrolase in rat kidney with a highly specific antibody raised in rabbits against purified SAH hydrolase from bovine kidney. This antibody crossreacts to almost the same extent with the SAH hydrolase from different species such as rat, pig, and human. Using light microscopy, SAH hydrolase was visualized by the biotin-streptavidin-alkaline phosphatase immunohistochemical procedure. SAH hydrolase immunostaining was observed in glomeruli and in the epithelium of the proximal and distal tubules. The collecting ducts of the cortex and medulla were homogeneously stained. By using double immunofluorescence staining and two-channel immunofluorescence confocal laser scanning microscopy, we differentiated the glomerular cells (endothelium, mesangium, podocytes) and found intensive staining of podocytes. Our results show that the enzyme SAH hydrolase is found ubiquitously in the rat kidney. The prominent staining of SAH hydrolase in the podocytes may reflect high rates of transmethylation. (J Histochem Cytochem 48:211-218, 2000)

Adenosylhomocysteinase↗
PubMed2000

Effect of the selective adenosine A1-receptor antagonist KW-3902 on tubuloglomerular feedback in radiocontrast-media-induced nephropathy in rats with chronic nitric oxide deficiency.

To study the possible mechanism of renoprotective effects of adenosine A1-receptor antagonist against radiocontrast media (RCM)-induced nephropathy, we investigated the effects of adenosine A1-receptor antagonist on tubuloglomerular feedback (TGF) activity prior to and following application of RCM in chronic NO-depleted rats. TGF in NO-depleted rats was significantly enhanced compared with that in normal rats. After RCM application, the enhanced TGF was continued. A selective adenosine A1-receptor antagonist, KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), inhibited the enhanced TGF. These results suggest that KW-3902 could inhibit TGF in chronic NO-depleted rats. Renoprotective effects by adenosine antagonists could be partly due to an inhibition of TGF via the blockade of the adenosine A1-receptor.

Animals↗
PubMed2000

Simple and sensitive binding assay for measurement of adenosine using reduced S-adenosylhomocysteine hydrolase.

BACKGROUND: Adenosine has been suggested to play an important role in the regulation of renal function. We developed a simple and sensitive binding assay for the detection of adenosine based on the displacement of [(3)H]adenosine from S-adenosylhomocysteine (SAH) hydrolase in its reduced form. METHODS: SAH hydrolase was purified to apparent homogeneity from bovine kidney by standard chromatographic methods. SAH hydrolase was converted in its reduced form, which had the advantage that the SAH hydrolase is enzymatically inactive. This reduced enzyme retains its ability to bind adenosine with high affinity. To determine adenosine in urine or tissues, samples must be deproteinized (e.g., with 10 g/L sulfosalicylic acid or 0.6 mol/L perchloric acid). RESULTS: The reduced SAH hydrolase bound adenosine with a dissociation constant of 33.0 +/- 2 nmol/L. Displacement of adenosine binding by the adenine 5'-nucleotides, adenine and hypoxanthine, required >1000-fold higher concentrations than adenosine itself. The intra- and interassay imprecision (CV) was <3.9% and 7.8%, respectively, and the values obtained showed acceptable correlation with those by HPLC. CONCLUSIONS: The highly sensitive adenosine-binding protein assay is a simple test that allows detection of adenosine in samples with small volumes without purification, and is in this respect superior to HPLC.

Adenosine↗
PubMed1999

Eukaliuric diuresis and natriuresis in response to the KATP channel blocker U37883A: micropuncture studies on the tubular site of action.

1. Systemic application of U37883A, a blocker of ATP sensitive potassium (KATP) channels, elicits diuresis and natriuresis without significantly altering urinary potassium excretion. 2. To elucidate tubular sites of action upstream to the distal nephron, micropuncture experiments were performed in nephrons with superficial glomeruli of anaesthetized Munich-Wistar-Frömter rats during systemic application of U37883A (1, 5 or 15 mg kg-1 i.v.). 3. The observed eukaliuric diuresis and natriuresis in response to U37883A at 15 mg kg-1 was accompanied by an increase in early distal tubular flow rate (VED) from 10 - 18 nl min(-1) reflecting a reduction in fractional reabsorption of fluid up to this site (FR-fluid) of 13%. The latter proposed an effect on water-permeable segments such as the proximal tubule which could fully account for the observed reduction in fractional reabsorption of Na+ up to the early distal tubule (FR-Na+) of 8% and the increase in early distal tubular Na+ concentration ([Na+]ED) from 35 - 51 mM whereas [K+]ED was left unaltered. 4. In comparison, furosemide (3 mg kg-1 i.v.), which acts in the water-impermeable thick ascending limb, elicited diuresis, natriuresis and kaliuresis which were associated with a fall in FR-Na+ of 10% with no change in FR-fluid, and a rise in [Na+]ED from 42 - 117 mM and [K+]ED from 1.2 - 5.7 mM with no change in VED. 5. Direct late proximal tubular fluid collections confirmed a significant inhibition of fluid reabsorption in proximal convoluted tubule in response to systemic application of U37883A. 6. These findings suggest that the diuretic and natriuretic effect upstream to the distal tubule in response to systemic application of U37883A involves actions on water-permeable segments such as the proximal convoluted tubule.

Adamantane↗
PubMed1999

Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline.

BACKGROUND: Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well-hydrated patients with mild-to-moderate renal insufficiency. METHODS: We studied 80 patients with pre-existing chronic renal insufficiency (creatinine > 1.5 mg/dl) who received more than 100 ml iopromide. Hydration (either oral or intravenous) started at least 24 h before and lasted until 24 h after CM application. In addition, patients were randomly assigned to receive either theophylline (810 mg daily) or placebo. Serum creatinine and creatinine clearance were measured before and for 3 days after CM application. Urine was collected to measure N-acetyl-beta-glucosaminidase (NAG) enzymuria for the same period. Sixty-four patients completed the entire study protocol (theophylline, n = 35 and placebo, n = 29). RESULTS: During the study period serum creatinine concentration and creatinine clearance did not change significantly in either group. Acute renal failure (increase of serum creatinine of at least 0.5 mg/dl) could be observed in two patients from the theophylline group (5.7%) and one from the placebo group (3.4%). The increase in NAG excretion reached statistical significance (P < 0.05) in the placebo group on days 2 and 3 after CM application. CONCLUSIONS: Our results indicate a role for adenosine in CM-induced tubulotoxicity. However, the glomerular filtration rate is preserved by hydration alone in these patients. The application of theophylline did not bring an additional benefit. The use of adenosine antagonists may be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g. congestive heart failure).

Acetylglucosaminidase↗
PubMed1999

Protective effects of endothelin antagonists in chronic renal failure.

The present study suggests that ET-1 is involved in the pathogenesis of uraemic cardiac hypertrophy and in the progression of renal failure in rats with subtotal nephrectomy examined after an intermediate period of 12 weeks of renal failure. Furthermore, proteinuria is reduced by the selective ETA receptor antagonist more than by the unselective ETAB receptor antagonist, without reducing the blood pressure. ET receptor blockade might preserve renal function by reduction of protein excretion. In addition, ET receptor antagonists influence the aldosterone system. In our animal studies, the medication was well tolerated. Our study results provide a possible therapeutic approach using ET receptor antagonists for cardiac hypertrophy and renal protein excretion by blockade of endogenous ET-1. Further human studies are needed to show whether this protection of the heart and kidney might influence the survival and life expectancy of patients suffering from chronic renal failure, of patients on dialysis or after kidney transplantation.

Animals↗
PubMed1999

Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of nitric oxide.

In rats with streptozotocin (STZ)-induced diabetes, the renal vasoconstrictor effect of adenosine is enhanced. We investigated the role of nitric oxide (NO) in the renal vascular response to exogenous and endogenous adenosine in control and STZ diabetic rats. Exogenous adenosine (0.01-100 nmol) injected into the abdominal aorta decreased renal blood flow (RBF) in a dose-dependent manner to a much greater extent in STZ rats than in control rats (P < 0.001). Inhibition of NO synthesis with Nomega-nitro-L-arginine (L-NNA, 30 micromol/kg iv) and with renal perfusion pressure controlled potentiated the adenosine-induced renal vasoconstriction to a significantly greater extent in control rats than in STZ rats. In control rats, L-NNA shifted the dose-response curve of exogenous adenosine-induced RBF reductions to the left by a factor of 32 [half-maximal effective dose (ED50), from 5.5 to 0.17 nmol adenosine, n = 6] and in STZ rats only by a factor of 4.6 (ED50, from 0.32 to 0.07 nmol adenosine, n = 6). The renal response to endogenous adenosine was assessed by the magnitude of the postocclusive reduction of RBF (POR) after a 30-s renal artery occlusion. POR was markedly enhanced in STZ rats (-67.8 +/- 3.8%, P < 0.001) compared with control rats (-38.8 +/- 4.3%). L-NNA markedly enhanced POR in control rats but did not increase POR in STZ rats. These findings demonstrate a greater potentiation of the adenosine-induced renal vasoconstriction in the presence of L-NNA infusion in control rats compared with STZ rats. We conclude that the increased vasoconstrictor sensitivity of the diabetic renal vasculature to adenosine is caused by a defective NO-dependent renal vasodilation of the afferent arteriole in diabetic rats.

Adenosine↗
PubMed1999

Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption.

An increase in Na+/glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a greater reduction in absolute and fractional reabsorption of Na+, Cl-, and K+ up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na+/glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.

Animals↗
PubMed1999

Dynamics of glial fibrillary acidic protein distribution in cultured glomerular podocytes and mesangial cells of the rat kidney.

Glial fibrillary acidic protein (GFAP) has recently been shown to be expressed in the glomerular podocytes and mesangial cells (MC) of kidney (Buniatian et al (1998) Biol Cell 90, 53-61). The different localization of GFAP in podocytes and MC has raised the question whether this might reflect specific cellular functions. To address this question, in the present study podocytes and MC in early (2, 3 day-old), prolonged (5, 7 day-old) and late (14, 21 day-old) primary cultures from out-growths of glomerular explants were used. Double-immunolabeling studies demonstrated that podocytes transiently acquire myofibroblastic features, characterized by the expression of smooth muscle alpha-actin (SMAA) and increased perinuclear reaction of GFAP in prolonged cultures. The morphological differentiation of cobblestone-like podocytes into process-bearing cells was followed by loss of the myofibroblastic marker, SMAA, de novo expression of desmin, and distribution of GFAP, vimentin and desmin into the processes. In late culture, GFAP and SMAA were nearly absent from the podocytes which maintained the cobblestone-like morphology. By contrast, the myofibroblastic features gained by MC during prolonged culturing increased with time. A myofibroblast-like cytoskeleton of podocytes and MC similar to that of healthy astrocytes suggest an increased spectrum of functional activities of these cells during the acquisition of myofibroblastic features. In addition, the present study provides a new combination of biochemical and biological features by which podocytes and MC can be distinguished in culture.

Actins↗
PubMed1998

Decreased HER-2 tyrosine kinase expression in rectal mucosa of FAP patients following low-dose sulindac chemoprevention.

As a part of the mechanisms of action in reversing FAP adenomas by the low-dose sulindac maintenance therapy (2 x 25 mg/patient per day), the extent of HER-2 proto-oncogene expression in the rectal mucosa seems to be of interest. Immunocytochemical analyses were performed in plasma and in rectal tissue of sulindac-treated FAP patients during an 18 months follow-up and compared with rectal tissue of patients with FAP, Crohn's disease, or rectal cancer or with healthy volunteers. HER-2 was significantly reduced and maintained in tissue under sulindac chemoprevention below base line levels of healthy individuals, but not in plasma. Therefore, a direct or indirect effect of sulindac as a tyrosine kinase inhibitor may be implicated. During NSAID treatment HER-2 protein expression as a prognostic tool seems to be of little clinical relevance.

Adenomatous Polyposis Coli↗
PubMed1998

Effects of ions on adenosine binding and enzyme activity of purified S-adenosylhomocysteine hydrolase from bovine kidney.

The present investigation was undertaken to determine the effect of various ions on the characteristics of S-adenosylhomocysteine (SAH) hydrolase from bovine kidney. The binding sites of [3H]-adenosine to purified SAH hydrolase were not influenced by phosphate, magnesium, potassium, sodium, chloride or calcium ions at physiological cytosolic concentrations. To test whether NAD+ in the SAH hydrolase is essential for adenosine binding, we prepared the apoenzyme by removing NAD+ with ammonium sulfate. The resulting apoenzyme did not exhibit any [3H]-adenosine binding. Since the apoenzyme was enzymatically inactive, it is suggested that adenosine binds to the active site and not to an allosteric site of the intact enzyme. The kinetics of the hydrolysis and the synthesis of SAH catalyzed by the enzyme SAH hydrolase were measured in the presence and absence of phosphate and magnesium. Phosphate increased the Vmax for both synthesis and hydrolysis. However, only the affinity of adenosine for SAH synthesis was significantly enhanced from 10.1+/-1.3 microM to 5.4+/-0.5 microM by phosphate. This effect was already maximal at a phosphate concentration of 1 mM. All other tested ions were without effect on the enzyme activity. Our results show that phosphate at physiological concentrations shifts the thermodynamic equilibrium of SAH hydrolase in the direction of SAH synthesis. These findings imply that SAH-sensitive transmethylation reactions are inhibited during renal hypoxia when intracellular levels of phosphate, adenosine, and SAH are elevated.

Adenosine↗
PubMed1998

Renal haemodynamic responses to exogenous and endogenous adenosine in conscious dogs.

1. Adenosine has been suggested to be the mediator of a metabolic feedback mechanism which transfers acute changes in the tubular load into opposite changes in renal blood flow (RBF). The goal of the present experiments was to assess the importance of endogenously formed adenosine as a 'homeostatic metabolite' during short-term changes in metabolic demand. 2. In nine chronically instrumented conscious foxhounds, both the direct effects of adenosine injections (10, 30 and 100 nmol) into the renal artery and the temporal changes of RBF after short renal artery occlusions (15, 30 and 60 s duration), the most widely used experimental model to study the metabolic feedback mechanism in vivo, were studied. 3. Intrarenal bolus injections of adenosine (10, 30 and 100 nmol) induced dose-dependent decreases of RBF (RBF: -34 +/- 5, -59 +/- 4 and -74 +/- 4 %, respectively). This vasoconstrictor effect of adenosine was significantly larger (RBF: -51 +/- 4, -68 +/- 4 and -83 +/- 3 %, respectively) when the dogs received a low salt diet. 4. The post-occlusive responses were characterized by a transient hyperaemia with no detectable drop of RBF below the preocclusion level. The post-occlusive responses were affected neither by changes in local angiotensin II levels, nor by intrarenal infusions of hypertonic NaCl or blockade of A1 adenosine receptors. 5. When intrarenal adenosine levels were elevated by infusion of the adenosine uptake inhibitor dipyridamole, a transient, although weak, post-occlusive vasoconstriction was detected. 6. In summary, the present data demonstrate that adenosine acts as a potent renal vasoconstrictor in the conscious dog. The endogenous production of adenosine during short-lasting occlusions of the renal artery, however, appears to be too small to induce a post-occlusive vasoconstrictor response of RBF. These results suggest that a metabolic feedback with adenosine as 'homeostatic metabolite' is of minor importance in the short-term regulation of RBF in the conscious, unstressed animal.

Adenosine↗
PubMed1998

Eukaliuric natriuresis and diuresis in response to disprocynium24: studies on the tubular site of action.

We previously described that 1,1'-diisopropyl-2,4'-cyanine (disprocynium24, DP24) exerts an eukaliuric diuresis and natriuresis in the anesthetized rat. The purpose of the present study was to localize the tubular site of action of DP24. Employing micropuncture experiments in anesthetized rats, we first tested the effect of systemic application of DP24 (300 microg/kg + 300 microg/kg h, i.v.) on whole kidney excretion rates as well as on fluid, sodium and potassium ion delivery to the early distal tubule (V(ED), Na+(ED), K+(ED)). It was found that the eukaliuric diuresis and natriuresis in response to DP24 was accompanied by a substantial increase in V(ED) and Na+(ED), suggesting a predominant tubular site of action upstream to the early distal tubule, most likely in the proximal tubule. DP24 caused a comparable fractional, although minor absolute increase in K+(ED) as compared to Na+(ED). Second, application of DP24 into the first surface loop of the proximal tubule significantly increased V(ED) and Na+(ED) at a concentration of about 10(-7) M, indicating that DP24 may act from the intratubular site. Third, microperfusion of tubular segments revealed that effects of DP24 on the proximal convoluted tubule and the loop of Henle accounted for about 70 and 30%, respectively, of its diuretic and natriuretic action upstream to the early distal tubule. With regard to the loop of Henle, the quantitative effect of DP24 on fluid and Na+ reabsorption proposed a predominant effect on the straight part of the proximal tubule rather than the thick ascending limb. Intratubular DP24 did not affect reabsorption in the distal tubule. In summary, the present findings indicate that: (1) the diuretic and natriuretic effect of DP24 resides predominantly in the proximal tubule, and (2) DP24 may act from the intratubular site. Since DP24 increased V(ED) and Na+(ED) without apparently affecting sodium or potassium ion transport in the distal tubule, the mechanism of the eukaliuric response remains unclear.

Animals↗