The Actions of Bradykinin and Eledoisin in the Canine Isolated Kidney: Relationships to Prostaglandins

1975 ◽  
Vol 49 (2) ◽  
pp. 125-131 ◽  
Author(s):  
J. C. McGiff ◽  
H. D. Itskovitz ◽  
N. A. Terragno

1. The effects of two vasodilator polypeptides, bradykinin and eledoisin, were studied in isolated blood-perfused canine kidneys before and after administration of indomethacin, an inhibitor of prostaglandin synthesis. Bradykinin, but not eledoisin, releases renal prostaglandins. 2. Before administration of indomethacin, bradykinin decreased urinary osmolality and increased free water clearance, whereas eledoisin did not affect the excretion of solute-free water. After administration of indomethacin, the renal vasodilator action of bradykinin was reduced but the vasodilator action of eledoisin was unaffected. 3. Fractional excretion of sodium was not affected by bradykinin before but was increased after administration of indomethacin. Reduction in glomerular filtration rate contributed to changes in sodium excretion produced by bradykinin and eledoisin. 4. The release of prostaglandins from the kidney by bradykinin amplifies the renal vasodilator action of the kinin and possibly mediates its effect on excretion of solute-free water.

1978 ◽  
Vol 55 (4) ◽  
pp. 335-339 ◽  
Author(s):  
A. L. Riley ◽  
T. C. Hagen ◽  
J. E. Stefaniak

1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin. 2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12–18% increase in glomerular filtration rate (GFR) by both kidneys. 3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance. 4. We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow.


1988 ◽  
Vol 255 (3) ◽  
pp. F391-F396 ◽  
Author(s):  
J. D. Firth ◽  
A. E. Raine ◽  
J. G. Ledingham

The effect of alteration in renal perfusion pressure on the response of the isolated perfused rat kidney to concentrations of alpha-human atrial natriuretic peptide (ANP) within the pathophysiological range has been examined. At a perfusion pressure of 90 mmHg ANP concentrations of 50, 200, and 1,000 pmol/l were without effect on any parameter tested. At a perfusion pressure of 130 mmHg 50 pmol/l ANP produced an increase of 3.13 +/- 0.68 mumol/min in sodium excretion (UNa V), compared with a fall of 0.33 +/- 1.04 mumol/min in controls (P less than 0.02); fractional excretion of sodium (FENa) rose by 1.45 +/- 0.36% vs. -0.12 +/- 0.47% (P less than 0.05); glomerular filtration rate (GFR) was unchanged. At 200 and 1,000 pmol/l larger changes in UNa V and FENa were seen; only at 1,000 pmol/l was a significant effect on GFR observed. In contrast, frusemide (furosemide) at concentrations of 10 and 100 mumol/l was natriuretic at both 90 and 130 mmHg, with lesser absolute but greater proportional changes being seen at the lower pressure. It was concluded 1) the response of the isolated kidney to ANP is critically dependent on perfusion pressure, 2) at elevated levels of perfusion pressure the isolated kidney can respond to levels of ANP within the upper physiological and pathophysiological range.


1983 ◽  
Vol 244 (2) ◽  
pp. F134-F139 ◽  
Author(s):  
S. Kaojarern ◽  
P. Chennavasin ◽  
S. Anderson ◽  
D. C. Brater

Indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) decrease solute excretion when administered acutely to normal subjects. We performed clearance studies during water loading of 10 normal volunteers and during hydropenia in eight additional subjects to determine the nephron site of this effect using indomethacin and carprofen as inhibitors of prostaglandin (PG) synthesis. Their administration decreased fractional excretion of sodium, chloride, and volume. During water loading, fractional clearance of free water decreased from 0.13 +/- 0.04 during the control study to 0.09 +/- 0.03 and 0.06 +/- 0.02 with indomethacin and carprofen, respectively. However, fractional delivery of solute to the dilution segment decreased in parallel such that free water clearance corrected for delivery did not change with either drug. In humans, therefore, the decrement in solute excretion that occurs with administration of NSAIDs occurs prior to the diluting segment. During hydropenia, free water reabsorption relative to osmolar clearance increased (P less than 0.01). In both studies, neither the marker of renal perfusion or of proximal nephron function changed with inhibition of PG synthesis. The data indicate that at the tubular level, NSAIDs increase solute reabsorption at the medullary segment of the thick ascending limb of the loop of Henle. Therefore, a physiologic role of renal prostaglandins at this nephron site is implied.


1972 ◽  
Vol 43 (2) ◽  
pp. 275-287 ◽  
Author(s):  
M. Epstein ◽  
D. C. Duncan ◽  
L. M. Fishman

1. The effects of 4–6 h of water immersion on the renal excretion of water and electrolytes were studied in thirteen normal male subjects in balance on a constant diet containing 150 mEq of Na and 100 mEq of K per day. Each subject was studied during a control period, consisting of quiet sitting, and during water immersion to the neck. 2. Immersion resulted in a natriuresis beginning within the first hour, with the rate of sodium excretion eventually exceeding that of the control period by 3–4-fold; potassium excretion also increased. Despite a progressively negative water balance during the immersion studies, urine flow was greater during the first 4 h and free water clearance was greater during the first 2 h of immersion than during the control study. 3. The demonstration of a highly significant increase in fractional excretion of sodium during immersion suggests that the natriuresis of water immersion is not attributable to changes in filtered sodium load. 4. The prompt onset of the natriuresis, the concomitant kaliuresis and the fact that aldosterone secretion under the conditions of study was probably already suppressed make it unlikely that the natriuresis of water immersion is mediated solely by decreases in aldosterone activity. 5. The data suggest that the natriuresis caused by water immersion is the result of decreased fractional reabsorption of sodium proximal to the renal diluting site. The mechanism whereby increased proximal tubular sodium rejection occurs in relation to immersion remains unclear.


1990 ◽  
Vol 32 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Joel Paulo R. Veiga ◽  
Rashida Khanam ◽  
Tânia T. Rosa ◽  
Luiz F. Junqueira Jr. ◽  
Plínio C. Brant ◽  
...  

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sb v (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.


2012 ◽  
Vol 303 (3) ◽  
pp. F420-F430 ◽  
Author(s):  
Yue Zhang ◽  
Kaiya L. Morris ◽  
Shannon K. Sparrow ◽  
Karen M. Dwyer ◽  
Keiichi Enjyoji ◽  
...  

Ectonucleoside triphosphate diphosphohydrolase-1 hydrolyzes extracellular ATP and ADP to AMP. Previously, we showed that CD39 is expressed at several sites within the kidney and thus may impact the availability of type 2 purinergic receptor (P2-R) ligands. Because P2-Rs appear to regulate urinary concentrating ability, we have evaluated renal water handling in transgenic mice (TG) globally overexpressing hCD39. Under basal conditions, TG mice exhibited significantly impaired urinary concentration and decreased protein abundance of AQP2 in the kidney compared with wild-type (WT) mice. Urinary excretion of total nitrates/nitrites was significantly higher in TG mice, but the excretion of AVP or PGE2 was equivalent to control WT mice. There were no significant differences in electrolyte-free water clearance or fractional excretion of sodium. Under stable hydrated conditions (gelled diet feeding), the differences between the WT and TG mice were negated, but the decrease in urine osmolality persisted. When water deprived, TG mice failed to adequately concentrate urine and exhibited impaired AVP responses. However, the increases in urinary osmolalities in response to subacute dDAVP or chronic AVP treatment were similar in TG and WT mice. These observations suggest that TG mice have impaired urinary concentrating ability despite normal AVP levels. We also note impaired AVP release in response to water deprivation but that TG kidneys are responsive to exogenous dDAVP or AVP. We infer that heightened nucleotide scavenging by increased levels of CD39 altered the release of endogenous AVP in response to dehydration. We propose that ectonucleotidases and modulated purinergic signaling impact urinary concentration and indicate potential utility of targeted therapy for the treatment of water balance disorders.


1987 ◽  
Vol 253 (5) ◽  
pp. F868-F873
Author(s):  
C. A. Gaillard ◽  
H. A. Koomans ◽  
A. J. Rabelink ◽  
E. J. Mees

We studied the effect of alpha-human natriuretic peptide (ANP, 100 micrograms iv) on renal sodium handling in eight healthy subjects before and after 7 days of indomethacin (50 mg 3 times a day). Sodium intake was 100 mmol/day. Prior to indomethacin, ANP caused a fourfold rise in sodium excretion over the first 20 min and a threefold rise in fractional sodium excretion. The clearance studies, performed during maximal water diuresis, showed increased fractional free water clearance and lithium clearance. Indomethacin caused marked sodium retention. Complete escape did not occur until the sixth day, when cumulative balance was 244 mmol (range 176-337). By this time renin and aldosterone were suppressed and fractional lithium and free water clearance reduced. The natriuretic effect of ANP was not attenuated, and the fractional excretion of sodium and chloride rose even more than without indomethacin. The reduction in lithium and free water clearance under indomethacin tended to be reversed by ANP. These data suggest that the natriuretic effect of ANP is not mediated by or dependent on renal prostaglandins. Indomethacin and ANP appear to have opposite effects on sodium excretion, maximal free water clearance, and lithium clearance.


2021 ◽  
Vol 10 ◽  
pp. 216495612110311
Author(s):  
Ewa Ogłodek ◽  
Wiesław Pilis, Prof.

Background Water-only fasting (WF) is a practice used to improve and maintain health. Objective The aim of the study was to show whether WF performed for 8 days may be a threat to the health and/or life of people undergoing this practice. Methods Twelve middle-aged men participated in the study. During the 8-day WF, the subjects ate no food except for drinking mineral water. Before and after WF, all subjects had a series of tests performed, beginning with the level of perceived stress and somatic measurements. The concentrations of creatinine, sodium (Na+), potassium (K+), total calcium (Ca), magnesium (Mg++), urea (U), uric acid (UA) and total protein were determined in this urine and in the serum. For these substances, the values ​​of clearance, renal filtration and fractional excretion were calculated. The osmotic clearance and free water clearance as well as the amount of daily urinary excretion of creatinine, Na+, K+, Ca, Mg++, U and UA were also calculated. Moreover, the concentration of glucose in the serum and the concentration of β-hydroxybutyrate in the plasma were determined. In urine, specific gravity, pH and osmolality were also measured. Results After 8 days of WF, the study showed a significant reduction in the level of perceived stress, weight loss, changes in body composition, dehydration, increased ketogenesis, hyperuricemia, decreased serum glucose concentration, and hyponatremia. These changes were accompanied by Na+, K+ and protein sparing, decreased serum Ca and Mg++ concentrations, and reduced daily volume of more acidic urine with elevated specific gravity. Conclusions After 8 days of WF, all subjects were found to remain safe and feel the sense of well-being. However, the appearance of the above-mentioned adverse metabolic effects, despite partially effective renal compensations, suggests that the further continuation of fasting intervention by the subjects would be detrimental to their body.


2002 ◽  
Vol 283 (4) ◽  
pp. E711-E721 ◽  
Author(s):  
Nina S. Stachenfeld ◽  
David L. Keefe

To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP) and body fluids, we suppressed endogenous estrogen and progesterone using the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n = 9, 25 ± 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n = 6, 26 ± 3). During GnRHa alone and with hormone treatment, we compared AVP and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml · min−1 · kg body wt−1), drinking (30 min, 15 ml/kg body wt), and recovery (60 min of seated rest). Plasma [E2] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P4] increased from 0.6 to 5.7 ng/ml during E/P and was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced osmotic AVP release threshold (275 ± 4 to 271 ± 4 mosmol/kg, P < 0.05), and E/P reduced the AVP increase in response during HSI (6.0 ± 1.3 to 4.2 ± 0.6 pg/ml at the end of HSI), but free water clearance was unaffected in either group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during E (0.8 ± 0.1 vs. 1.2 ± 0.2 ng ANG I · ml−1 · h−1) but not after HSI or recovery. PRA was greater than GnRHa during E/P at baseline (1.1 ± 0.2 vs. 2.5 ± 0.6) and after HSI (0.6 ± 0.1 vs. 1.1 ± 1.1) and recovery (0.5 ± 0.1 vs. 1.3 ± 0.2 ng ANG I · ml−1 · h−1). Baseline fractional excretion of sodium was unaffected by E or E/P but was attenuated by the end of recovery for both E (3.3 ± 0.6 vs. 2.4 ± 0.4%) and E/P (2.8 ± 0.4 vs 1.7 ± 0.4%, GnRHa alone and with hormone treatment, respectively). Fluid retention increased with both hormone treatments. Renal sensitivity to AVP may be lower during E due to intrarenal effects on water and sodium excretion. E/P increased sodium retention and renin-angiotensin-aldosterone stimulation.


1977 ◽  
Vol 55 (1) ◽  
pp. 105-110 ◽  
Author(s):  
Serge Carrière ◽  
Michèle Gagnan-Brunette

Sodium ferrocyanide was used to measure the intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in remaining kidneys of dogs, 10 d after contralateral nephrectomy. It was first demonstrated that the renal function of both kidneys in situ was comparable. Following right nephrectomy, the urine volume, p-aminohippuric acid clearance, creatine clearance, osmolar clearance, fractional excretion of potassium, and sodium excretion of the left kidney increased. Fractional excretion of sodium, free water clearance, and filtration fraction remained unchanged. Following that 10-d period, left kidney weight exceeded that of the previously removed contralateral kidney by 50%, indicating that most of the compensatory hypertrophy had already occurred. No significant difference in the length of the proximal tubule nor in the diameter of the glomeruli of superficial (SUP) and juxtamedullary (JM) nephrons of either kidney could be demonstrated. Most importantly, the ratio of radioactivity in the SUP/JM nephrons of the residual kidney was comparable with that previously observed in normal dog kidneys. Thus, the increase in total kidney GFR is explained through a proportional increase in the SNGFR of the SUP and JM nephrons.


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