Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity

1981 ◽  
Vol 241 (2) ◽  
pp. F175-F185 ◽  
Author(s):  
R. Safirstein ◽  
P. Miller ◽  
S. Dikman ◽  
N. Lyman ◽  
C. Shapiro
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Urine Volume ◽  
Distal Tubule ◽  
Urine Osmolality ◽  
Solute Content ◽  
Cisplatin Nephrotoxicity

We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.

Micropuncture study of the superficial nephron of Perognathus penicillatus

1981 ◽  
Vol 241 (6) ◽  
pp. F612-F617
Author(s):  
E. J. Braun ◽  
D. R. Roy ◽  
R. L. Jamison
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Urine Osmolality ◽  
Small Rodent ◽  
Micropuncture Study ◽  
Single Nephron ◽  
Average Body

A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.

Effects of blood pH changes on potassium excretion in the dog

1962 ◽  
Vol 202 (4) ◽  
pp. 768-772 ◽  
Author(s):  
Charles Toussaint ◽  
Pierre Vereerstraeten
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Distal Tubule ◽  
Potassium Excretion ◽  
Ph Changes ◽  
Blood Ph ◽  
Ph Level

K+ excretion rate was measured at normal as well as at rising plasma K+ concentration in intact, in K-depleted, and in acetazolamide-treated dogs submitted to acute blood pH changes. The results indicate that, for any given value of glomerular filtration rate, K+ excretion rate is determined by at least three factors: 1) plasma K+ concentration, 2) blood pH level, and 3) presumably, the H+ gradient across the luminal border of the distal tubule. The data further suggest that most of the filtered K+ is reabsorbed by the proximal tubule, even in conditions of high filtered loads.

Localization of alpha 2-adrenoceptor-mediated increase in renal Na+, K+, and water excretion

1987 ◽  
Vol 252 (6) ◽  
pp. F1016-F1021 ◽  
Author(s):  
B. Stanton ◽  
E. Puglisi ◽  
M. Gellai
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Water Transport ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Water Excretion ◽  
Arterial Blood ◽  
Adrenoceptor Agonist

Free-flow micropuncture and clearance studies were conducted in male Sprague-Dawley rats to investigate the effects of alpha 2-adrenoceptor stimulation on Na+, K+, and water transport along the nephron. Intravenous infusion of the selective alpha 2-adrenoceptor agonist B-HT 933 at 1 mg X kg-1 X h-1 increased urinary flow rate from 16.2 +/- 3.6 to 84.8 +/- 11.9 microliter/min, fractional excretion of Na+ from 1.36 +/- 0.31 to 3.57 +/- 0.52%, and fractional excretion of K+ from 26.9 +/- 3.0 to 42.3 +/- 2.2%, The diuresis, saluresis, and kaliuresis were not the result of increases in glomerular filtration rate or mean arterial blood pressure. Urine osmolality decreased from 1,126 +/- 177 to 325 +/- 33 mosmol/kg water and in 8 of the 11 animals studied B-HT 933 decreased urine osmolality to hyposmotic levels, suggesting a possible interaction between the alpha 2-adrenoceptor agonist and vasopressin. The alpha 2-adrenoceptor antagonist yohimbine (0.25/mg bolus, iv) inhibited the diuresis, saliuresis, and kaliuresis. In micropuncture studies, B-HT 933 was without effect on single-nephron glomerular filtration rate or on Na+, K+, and water transport along the superficial proximal tubule, loop of Henle, or distal tubule. Thus stimulation of alpha 2-adrenoceptors increases Na+, K+, and water excretion by inhibiting tubule reabsorption of these substances at nephron sites beyond the superficial distal tubule, most likely by the collecting tubule.

Chlorothiazide effect on feedback-mediated control of glomerular filtration rate

1989 ◽  
Vol 257 (1) ◽  
pp. F137-F144 ◽  
Author(s):  
M. D. Okusa ◽  
A. E. Persson ◽  
F. S. Wright
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Feedback System ◽  
Sprague Dawley ◽  
Single Nephron ◽  
The Difference ◽  
Tubule Fluid

We examined the effect of chlorothiazide (CTZ) on the tubuloglomerular (TG) feedback system in anesthetized Sprague-Dawley rats. During infusion of CTZ (0.25 mg.kg body wt-1.min-1) we found that whole kidney glomerular filtration rate (GFR) decreased by 19% (1.0 +/- 0.1 vs. 0.8 +/- 0.1 ml/min; P less than 0.005). To asses the activity of the TG feedback system during CTZ administration we compared measurements of single-nephron (SN)GFR from tubule fluid sampled separately at proximal and distal sites. During CTZ administration, distally measured SNGFR decreased significantly by 16% (27.3 +/- 1.3 vs. 22.9 +/- 1.1 nl/min; P less than 0.025), whereas proximally measured SNGFR was unchanged. Thus the difference in SNGFR between proximal and distal determination increased during CTZ infusion (4.7 +/- 0.7 vs. 7.7 +/- 0.7 nl/min; P less than 0.025), indicating that CTZ suppresses GFR by TG feedback. Na, K, and Cl concentrations measured in the late proximal tubule fluid during control and CTZ infusions were similar. In early distal tubule fluid samples K and Cl concentrations were unaffected by CTZ infusion, whereas Na concentrations increased by 32% (47.9 +/- 2.7 vs. 63.1 +/- 2.4 mM; P less than 0.001). Proximal tubule microperfusion with 1.0 mM CTZ decreased transport rates of Na and water by approximately 40%, whereas the transport rate of Cl was not affected. In conclusion our results indicate that CTZ reduces GFR by activating TG feedback. The mechanism by which this occurs is in part due to an increase in the strength of the signal.

Tubular site(s) of action of atrial natriuretic peptide in the rat

1988 ◽  
Vol 255 (2) ◽  
pp. F313-F316 ◽  
Author(s):  
T. A. Fried ◽  
R. W. Osgood ◽  
J. H. Stein
Keyword(s):  
Glomerular Filtration Rate ◽  
Atrial Natriuretic Peptide ◽  
Glomerular Filtration ◽  
Natriuretic Peptide ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Synthetic Analogue ◽  
Papillary Collecting Duct ◽  
Atrial Natriuretic

With micropuncture techniques, the present study examined the delivery of chloride to the superficial late distal tubule and the base and tip of the papillary collecting duct in rats treated with either Wy 47663, a synthetic analogue of atrial natriuretic peptide (ANP), or vehicle alone. Whole kidney glomerular filtration rate (GFR) and single-nephron glomerular filtration rate were not significantly different between the two groups. Late distal tubule chloride delivery was also not different between ANP- (5.71 +/- 1.15%) and vehicle- (6.28 +/- 1.12%) treated animals. However, fractional delivery to the base of the papillary collecting duct was significantly greater in the ANP-treated rats (14.37 +/- 1.98%) compared with vehicle-treated rats (7.32 +/- 1.47%). Tip papillary collecting duct delivery was also significantly greater in the ANP-treated rats (1.97 +/- 1.96 vs. 3.09 +/- 0.60%). In addition, the percent of chloride delivered that was reabsorbed along the papillary collecting duct was significantly less in the ANP-treated rats. In conclusion, ANP inhibits reabsorption in some tubular segments between the superficial late distal tubule and papillary collecting duct base as well as in the accessible portion of the papillary collecting duct.

Micropuncture localization of the natriuretic effect of interleukin 1

1989 ◽  
Vol 256 (5) ◽  
pp. F810-F813 ◽  
Author(s):  
D. E. Kohan ◽  
C. A. Merli ◽  
E. E. Simon
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Interleukin 1 ◽  
Distal Tubule ◽  
Sodium Reabsorption ◽  
Natriuretic Effect ◽  
Papillary Collecting Duct

Interleukin 1 (IL-1) has been demonstrated to elicit an increase in renal sodium excretion. This effect occurs in the absence of any increase in the filtered load of sodium, raising the possibility of an IL-1-mediated decrease in tubule sodium reabsorption. To localize the nephron segment(s) responsible for the natriuretic effect of IL-1, we performed micropuncture experiments on rats. Intravenous IL-1 administration caused a marked increase in sodium excretion that was not accompanied by changes in glomerular filtration rate or systemic blood pressure. Single-nephron glomerular filtration rate and fractional and absolute delivery of sodium to the late proximal and mid-distal tubule were not affected by IL-1. Fractional delivery of sodium to the early and late papillary collecting duct, however, was significantly enhanced by IL-1 administration. Sodium reabsorption was inhibited along the papillary collecting duct. These findings demonstrate that the natriuretic effect of IL-1 is due, at least in part, to inhibition of collecting duct sodium reabsorption.

Electrolyte handling by the superficial nephron of the rabbit

1986 ◽  
Vol 250 (4) ◽  
pp. F590-F595 ◽  
Author(s):  
N. L. Wong ◽  
S. J. Whiting ◽  
C. L. Mizgala ◽  
G. A. Quamme
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Concentration Ratio ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Mean Value ◽  
Loop Of Henle ◽  
Collection Site ◽  
Micropuncture Study ◽  
The Mean

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.

Sodium and Water Excretion in Nephrotic Patients: Effects of Changes in Renal Haemodynamics

1990 ◽  
Vol 79 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Michael Allon ◽  
Charles B. Pasque ◽  
Mariano Rodriguez
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Sodium Reabsorption ◽  
Plasma Volume Expansion ◽  
Water Excretion ◽  
Significant Change

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.

Meclofenamate and urine concentration with and without exposure of the renal papilla

1981 ◽  
Vol 240 (5) ◽  
pp. F423-F429 ◽  
Author(s):  
R. J. Roman ◽  
C. Lechene
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Renal Papilla ◽  
Arterial Blood ◽  
Pelvic Urine

The recent finding that inhibitors of prostaglandin synthesis prevent the fall in urine concentration produced by papillary exposure challenges the hypothesis that contact between the pelvic urine and papilla is essential to the renal concentrating process. The present study examines the change in urine osmolality produced by exposure of the renal papilla in rats given meclofenamate. In control animals urine osmolality(Uosmol) decreased 57% after 2 h of exposure of the renal papilla. In rats given meclofenamate 4 mg/kg urine osmolality increased 16%, urine flow decreased 30%, and glomerular filtration rate was unchanged in the nonexposed kidney. Meclofenamate, however, did not alter the decrease in Uosmol seen in the kidney with the exposed papilla. Meclofenamate 10 mg/kg was also ineffective in preventing the fall in urine osmolality produced by papillary exposure, although this higher dose decreased glomerular filtration rate and arterial blood pressure. These results are consistent with the finding that pelvic urine urea is important to the urinary concentrating process and with the hypothesis that urine osmolality falls after papillary exposure because contact between pelvic urine and papilla is interrupted.

Effect of prolonged bodily hydration on the renal concentrating operation

1961 ◽  
Vol 16 (5) ◽  
pp. 815-818 ◽  
Author(s):  
Myong Cho Yoon ◽  
Suk Ki Hong
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Intramuscular Injection ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Mechanical Deformation ◽  
Urine Samples ◽  
Healthy Men ◽  
Subsequent Period ◽  
Consistent Change

The maximal renal concentrating ability was studied in six healthy men while 150 ml water/kg body wt. was forced daily for 9 days. The maximally concentrated urine samples were obtained after intramuscular injection of 5 units of surgical Pituitrin on the 3rd, 6th, and 9th day of the forced hydration period. The renal concentrating ability was already reduced on the 3rd day of the forced hydration, and there was very little further reduction during the subsequent period. All urinary constituents lost concentration in parallel. The rates of excretion of various urinary constituents through maximally concentrated urine did not show any consistent change. Moreover, all impairments were reversible and were not accompanied by any alteration in the glomerular filtration rate. It is thus considered that the observed reduction in renal concentrating ability during the forced hydration period is due to the reduction of tubular function. It is postulated that the collecting duct undergoes a certain mechanical deformation during the forced hydration period and, hence, is not able to perform the concentrating operation as much as it would do otherwise. Submitted on August 10, 1961

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