Biomedical subjects

U Honrath

Publications and source records attributed to U Honrath.

34 records · Page 2Linked to original sources

PubMed1987

Effects of amiloride in the medullary collecting duct of rat kidney.

The in vivo microcatheterization technique was used to study amiloride-induced transport alterations in the inner medullary collecting duct. Amiloride treated rats (0.1 mg/hr) had significant diuresis and natriuresis, as well as antikaliuresis, compared to untreated controls. The relative decrease in potassium excretion was associated with a significant rise in plasma potassium concentration. Net sodium transport in the duct was decreased from 83 + 3 to 46 + 6 per cent of delivered load, as a result of amiloride treatment. Smaller, but statistically significant, reductions (P less than 0.01) were seen for fluid and chloride reabsorptions (from 66 + 3 to 51 + 4%, and from 72 + 4 to 52 + 5%, respectively). Potassium reabsorption increased from 15 + 8 to 61 + 6% of delivered load. The data indicated that amiloride natriuresis is determined primarily by inhibition of sodium reabsorption in the medullary collecting duct, probably due to blockade of a specific Na channel. The antikaliuresis, on the other hand, appears to be due to inhibition of secretion both in upstream nephron segments and in the duct itself.

Amiloride↗

PubMed1987

Collecting duct function in cis-platinum nephrotoxicity.

Microcatheterization was used to study the effect of cis-platinum nephrotoxicity on inner medullary collecting duct function in anaesthetized rats. Osmolality of collecting duct fluid increased from the beginning to the end (papillary tip) of the collecting duct by only 69 +/- 11 mosmol/kg in cis-platinum treated rats (at 5-6 days) compared with 306 +/- 75 mosmol/kg in sham controls (p less than 0.01). Tubular fluid to plasma inulin concentration ratio was reduced at the beginning and end of the collecting duct. Tubular fluid sodium, chloride, and potassium concentrations were lower at the papillary tip in cis-platinum treated rats (p less than 0.01). The results indicate that collecting duct water reabsorption is reduced, but electrolyte reabsorption is normal (or even increased) in cis-platinum nephrotoxicity. Papillary tissue sodium chloride concentration was reduced in cis-platinum treated rats. We conclude that the characteristic decrease in urine concentrating ability in cis-platinum nephrotoxicity is not primarily the result of an intrinsic abnormality in collecting duct function but is secondary to decreased papillary hypertonicity resulting from impaired function in more proximal nephron segments, presumably the pars recta of the proximal tubule and the loop of Henle where previous studies have demonstrated abnormal function.

Animals↗

PubMed1987

Renal responses to saline and atrial natriuretic factor infusions in Dahl rats.

Weanling Dahl rats of the salt-sensitive and salt-resistant strains were kept either on a low salt diet for 10-15 weeks, or the diet was supplemented with 7% NaCl for the last 30 days. Animals were anesthetized and the renal responses to acute saline infusion and infusion of synthetic atrial natriuretic factor (ANF) were studied on both dietary regimens. Arterial blood pressures of sensitive and resistant groups were not different on the low salt intake. As expected, addition of dietary salt increased pressure markedly in the sensitive animals. Resistant rats also had smaller, but statistically significant, increases in pressure. On the low salt diet, salt-sensitive rats showed a larger renal response to saline infusion, whereas on the high salt diet there were no significant differences between strains. The responses to ANF infusion were not different between groups on either diet, although NaCl feeding potentiated the natriuresis and diuresis. Under the conditions of the present experiments there was, therefore, no indication that Dahl salt-sensitive rats had a relative inability to respond either to an acute saline load or to exogenous ANF administration.

Animals↗

PubMed1987

Effect of vasopressin analogue (dDAVP) on potassium transport in medullary collecting duct.

The microcatheterization technique was used to examine electrolyte transport in the medullary collecting duct of two groups of anesthetized rats during water diuresis and during a second experimental phase with 1-desamino-8-D-arginine vasopressin (dDAVP) administration or continued water diuresis. Potassium reabsorption of 53-61% of the delivered load was consistently observed in the medullary collecting duct during water diuresis. During dDAVP administration, urinary potassium excretion doubled, and there was no net potassium transport (reabsorption or secretion) in the medullary collecting duct. The change in potassium transport in medullary collecting duct from water diuresis to antidiuresis (dDAVP) was sufficient to account for the increase in urinary potassium excretion. Changes in flow rate, luminal sodium concentration, or collecting duct sodium reabsorption could not account for the changes in potassium transport in the collecting duct during dDAVP. The results are interpreted as indicating that dDAVP stimulates potassium entry (secretion) into the medullary collecting duct, probably by a direct effect. This action of antidiuretic hormone appears to be important in maintaining potassium homeostasis during changing water balance.

Animals↗

PubMed1986

Effect of acetylcholine and secretin on medullary collecting duct function in the rat.

Microcatheterization was used to study the effect of renal arterial infusion of acetylcholine or secretin on medullary collecting duct function in anaesthetized rats. Acetylcholine infusion was associated with natriuresis and increased sodium delivery to, and decreased reabsorption in, the collecting duct. No changes from control function were found with secretin. Renal blood flow was increased with acetylcholine (+82%, p less than 0.001), but unchanged with secretin (+15%, nonsignificant). We conclude that acetylcholine natriuresis is due to inhibition of tubular reabsorption of sodium in the medullary collecting duct, as well as in upstream nephron segments. While the latter may be hemodynamically mediated, the former indicates a direct transport effect of the hormone in the terminal nephron segment.

Absorption↗

PubMed1986

Atrial natriuretic factor inhibits sodium transport in medullary collecting duct.

Characteristics of sodium transport in the inner medullary collecting duct were determined in anesthetized rats before and during intravenous infusion of synthetic atrial natriuretic factor (atriopeptin II). Infusion of the factor was associated with increased sodium delivery and reduced fractional reabsorption in the duct. Increasing delivery to the same extent by KCl infusion had no effect on fractional reabsorption. The results demonstrate that atrial natriuretic factor has a specific inhibitory effect on net sodium transport in this part of the nephron. The mechanism of this inhibition may involve induction of sodium permeability and consequent backflux into the tubular lumen.

Absorption↗

PubMed1983

Thiazide diuretic effect on medullary collecting duct function in the rat.

The distal convoluted tubule is thought to be the principal site of action of thiazide diuretics, but, to our knowledge, there are no studies of their possible effects on collecting duct transport. Microcatheterization of the inner medullary collecting duct (IMCD) was carried out in rats undergoing a modest diuresis, natriuresis, and chloriuresis from hydro-chlorothiazide (2 mg/kg/hr) and in normal controls. Delivery of fluid, sodium, and chloride to the beginning of the IMCD was increased, but not significantly, while the load remaining at the papillary tip (end) of the duct was increased markedly by hydrochlorothiazide. Chloride reabsorption in the IMCD was affected most markedly; the chloride reabsorption between the beginning and end of the duct, as a fraction of the delivered load, was reduced from 70.4 +/- 5.4% in controls to insignificant amounts with hydrochlorothiazide (8.2 +/- 11.5%, P less than 0.001). The fraction of delivered sodium reabsorbed along the collecting duct was decreased from 78.5 +/- 4.9% in controls to 37.2 +/- 12.4% (P less than 0.005) in thiazide-treated rats and fluid reabsorption was decreased from 59.4 +/- 4.0% in controls to 31.9 +/- 5.1% (P less than 0.005). Small but significant potassium secretion into the IMCD occurred with hydrochlorothiazide, probably secondary to the marked increase in potassium delivery to the duct. Increased potassium excretion could account for a maximum of 50% of chloriuresis with hydrochlorothiazide. The observation that thiazide diuretics decrease chloride, sodium, and fluid reabsorption in the medullary collecting duct, like the recently demonstrated inhibitory effect of furosemide on this nephron segment, has significant implications for the rationale for diuretic use.

Animals↗

PubMed1983

Tissue catecholamines in obstructive nephropathy and acute uremia in the rat.

Previous studies have shown that the 24-h unilateral ureteral obstructed kidney (UUO) responds to acute renal denervation after relief of obstruction with an increase in glomerular filtration rate (GFR), renal plasma flow (RPF), natriuresis, and diuresis, while the 24-h bilateral ureteral obstructed kidney (BUO), undergoing postobstructive diuresis after relief of obstruction, shows no response to acute denervation. In the present study, renal tissue norepinephrine (NE) content and concentration were found to be markedly decreased in the BUO kidney suggesting partial renal denervation, while renal NE content was normal in the UUO kidney. The decrease in renal NE content in the BUO kidney was organ specific since myocardial NE was not affected, and was not due to acute uremia, since rats made uremic by 24 h of total intravenous urine reinfusion showed no change in renal NE content. Renal dopamine content was markedly increased in the UUO kidney, perhaps as a result of renal decarboxylation of dopa and failure of excretion, while renal and myocardial epinephrine content were increased in the BUO and urine reinfused groups, both of which were subjected to the stress of acute uremia. The decrease in renal NE content in the kidney undergoing postobstructive diuresis after relief of 24-h BUO probably indicates damage to sympathetic nerve terminals by high intrarenal pressure during BUO and suggests that partial renal denervation could contribute to the functional changes observed in this experimental model.

Acute Disease↗

PubMed1983

Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition.

The effect of furosemide on inner medullary collecting duct chloride reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of chloride, sodium, and water reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamate before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis, and diuresis. Reduced delivery of sodium and chloride to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. The results indicate that furosemide inhibits medullary collecting duct reabsorption of chloride, sodium, and water in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.

Animals↗

PubMed1982

Prostaglandin synthesis inhibition during volume expansion: collecting duct function.

The aim of this study was to examine the possible role of renal prostaglandins in the response of the inner medullary collecting duct (IMCD) to acute volume expansion. Collecting duct microcatheterization and clearance studies were carried out in anesthetized rats, volume-expanded with isotonic Ringer's solution. In volume-expanded control animals, there was no significant sodium or chloride reabsorption between the beginning and end (papillary tip) of the IMCD. Administration of indomethacin or meclofenamate prior to and during volume expansion in two other groups of rats resulted in significant water, sodium, and chloride reabsorption along the IMCD and markedly blunted the diuretic, natriuretic and chloriuretic response to volume expansion. Because delivery to the beginning of the duct was not significantly decreased, enhanced reabsorption in the IMCD largely accounted for the decrease in natriuresis and chloriuresis. Inner medullary tissue fluid chloride concentration increased after inhibition of prostaglandin synthesis. The results indicate that renal prostaglandins, perhaps by directly decreasing sodium chloride reabsorption, have an important role in the decrease in collecting duct reabsorption of sodium and chloride observed with acute volume expansion.

Animals↗

PubMed1981

Effect of renal denervation, furosemide, and acute saline loading on postobstructive diuresis in the rat.

The effect of acute or chronic renal denervation, furosemide, or acute saline loading on the postobstructive diuresis (POD) which occurs after relief of 24-h bilateral ureteral obstruction (BUO) was studied in anaesthetized rats. Acute renal denervation during POD 1--2 h after relief of BUO had no effect on glomerular filtration rate of sodium, potassium, water, or solute excretion, in contrast with its natriuretic and diuretic effect in sham-operated rats. Intravenous furosemide or acute saline loading caused a further marked increase in sodium and water excretion during POD, demonstrating the ability of the kidney undergoing POD to respond to other types of natriuretic stimuli. Chronic renal denervation prior to BUO had no effect on subsequent POD. The lack of response of the BUO kidney undergoing POD to acute denervation contrasts with the changes in renal function following denervation of the unilateral postobstructive kidney. The results indicate that the kidney undergoing POD after relief of BUO may be functionally denervated and suggest that inhibition of renal nerve activity could contribute to the pathophysiology of POD.

Animals↗

PubMed1980

Lack of effect of chronic renal denervation on altered sodium reabsorption during increased ureteral pressure.

The role of the renal nerves in the altered sodium reabsorption which occurs during increased ureteral pressure was studied using clearance techniques in anaesthetized rats undergoing diuresis induced by isotonic saline infusion. In rats with a sham denervated kidney, an ipsilateral increase in ureteral pressure to 20 cm H2O resulted in a marked and significant decrease in sodium and water excretion, increased fractional sodium reabsorption, and increased urine osmolality with no significant change in glomerular filtration rate. A similar significant ipsilateral increase in tubular reabsorption of sodium occurred in rats with chronically denervated kidneys during increased ureteral pressure. The changes in tubular reabsorption were rapidly reversible after return of ureteral pressure to normal. These experiments indicate that enhanced tubular reabsorption of sodium during an ipsilateral increase in ureteral pressure is not mediated by increased renal nerve activity. During the antinatriuresis of increased ureteral pressure there was a decrease in the fractional reabsorption of sodium from the opposite normal kidney. The role of the renal nerves in this compensatory change in function in the opposite kidney was studied in two further groups of animals. The renal response to a contralateral increase in ureteral pressure was similar in denervated and sham-denervated kidneys. The results indicate that altered renal nerve activity, through ipsilateral or contralateral renorenal reflexes, is not responsible for the changes in tubular reabsorption of sodium which occur during increased ureteral pressure induced by partial ureteral obstruction.

Absorption↗

PubMed1979

Circulating natriuretic and kaliuretic factors in acute uremia: the role of the kidney.

The role of the kidney as a source or as the excretory route for natriuretic and kaliuretic factors present in acute uremia was studied using the technique of isovolemic cross-circulation in 49 pairs (eight groups) of anaesthetized rats. Marked and similar natriuresis, kaliuresis, and diuresis occurred in recipients undergoing cross-circulation with donors subjected to either bilateral nephrectomy or total intravenous urine reinfusion for 18 h previously, and were not seen with sham-operated donors. Similar and significant, but less marked, changes occurred in two groups with bilateral nephrectomy or urine reinfusion of only 3 h duration. Urea-loaded normal donors caused a natriuresis and kaliuresis which was similar to the two 18-h uremic donor groups. When donor animals were sodium depleted prior to bilateral nephrectomy the natriuretic response in the recipients was significantly reduced. The results indicate that the kidney is not necessary for the rapid appearance of natriuretic and kaliuretic activity in the blood of acutely uremic animals, and that such activity results from the retention of factors of extrarenal origin. Natriuresis and kaliuresis result from inhibition of tubular reabsorption and are not dependent on changes in glomerular filtration or renal hemodynamics. Pitressin or aldosterone levels. Urea appears to be a major component of the circulating natriuretic and kaliuretic activity in acute uremia but evidence of other factors was also obtained.

Acute Disease↗

PubMed1979

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.

Animals↗

PubMed1978

Cross-circulation study of natriuretic factors in rats with reduced nephron mass.

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2-3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.

Animals↗

PubMed1976

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.

Adenosine Triphosphatases↗