Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog

Re-collection micropuncture and simultaneous clearance studies were performed in thyroparathyroidectomized (TPTX) dogs to evaluate the effects of the acute administration of parathyroid hormone (PTH) on bicarbonate reabsorption. The i.v. administration of PTH from 74 to 94 U/hr reduced proximal fractional reabsorption (FRHCO3) from 0.28 +/- 0.03 to 0.14 +/- 0.03 (P less than 0.005) and absolute bicarbonate reabsorption (THCO3) from 556 +/- 126 to 255 +/- 73 pmoles/min (P less than 0.05), whereas there were no changes in PCO2 (37.0 +/- 1.4 leads to 37.2 +/- 1.4 mm Hg, P greater than 0.90), plasma bicarbonate (PHCO3) (18.5 +/- 0.4 leads to 18.3 +/- 0.4, P less than 0.60), single nephron glomerular filtration rate (102.2 +/- 15;9 leads to 90.1 +/- 10.3 nl/min, P greater than 0.40), serum ultrafilterable phosphate concentration (SUFp) (1.71 +/- 0.13 leads to 1.83 +/- 0.12 mmoles/liter, P greater than 0.25), or serum ultrafilterable calcium (SUFCa) (1.85 +/- 0.05 leads to 1.88 +/- 0.05 mEq/liter, P greater than 0.60). PTH also reduced proximal fractional fluid (and sodium) reabsorption (0.40 +/- 0.04 leads to 0.28 +/- 0.08, P less than 0.05) while TFHCO3 did not change (20.5 +/- 0.4 leads to 20.8 +/- 0.4 mmoles/liter) indicating a rejection of bicarbonate proportional to the inhibition in tubular fluid transport. The invariable reduction in proximal bicarbonate reabsorption did not uniformly result in an increased urinary bicarbonate concentration.     

Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat

Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.     

Chronic tonsillitis

1. Maintenance of phosphate homeostasis is essential for energy producing and oxygen delivery systems, particularly, when the energy requirements are increased in certain conditions, such as septicaemia. We investigated the phosphaturic response to parathyroid hormone (PTH) in endotoxin (ETx)-treated rats in order to clarify the renal regulation of phosphate excretion during endotoxaemia. 2. Wistar rats that had undergone thyroparathyroidectomy were challenged with either Escherichia coli ETx (n = 8) or saline vehicle (n = 9). Thirty-minute renal clearance tests were done before and after PTH infusion. Rats infused with saline instead of PTH served as time controls for the ETx- (n = 7) and saline-treated (n = 8) rats. 3. In time control rats, ETx administration enhanced phosphate excretion progressively and this was associated with an obvious increase in the level of kidney adenosine 3', 5'-cyclic mono-phosphate (P < 0.005) compared with levels following saline vehicle administration. However, this phosphaturia in late-phase endotoxaemia was not observed in rats infused with PTH; ETx, but not saline vehicle, blunted the PTH-mediated increase in phosphate excretion (P < 0.005). Increased urinary noradrenaline and constant dopamine excretion were observed in endotoxaemic rats. Endotoxin administration produced marked metabolic acidosis and hypocapnia in comparison with the administration of the saline vehicle. 4. To test whether renal tubular sensitivity to parathyroid hormone related-protein (PTHrP) was enhanced during endotoxaemia, phosphaturic response to PTHrP in ETx- (n = 7) and saline-treated rats (n = 7) was examined. Parathyroid hormone related-protein infusion produced phosphaturia in both groups. However, the severity of the phosphaturia after PTHrP infusion was less in ETx-than in saline-treated rats. 5. In summary, although ETx administration causes a progressive increase in phosphate excretion in the absence of PTH, this is overcome by the antiphosphaturic effect of ETx, attenuating PTH-mediated phosphaturia after PTH infusion.     

Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.     

The renal handling of parathyroid hormone. Role of peritubular uptake and glomerular filtration

The mechanisms of uptake of parathyroid hormone (PTH) by the kidney was studied in anesthetized dogs before and after ureteral ligation. During constant infusion of bovine PTH (b-PTH 1-84), the renal arteriovenous (A-V) difference for immunoreactive PTH (i-PTH) was 22+/-2%. After ureteral ligation and no change in renal plasma flow, A-V i-PTH fell to 15+/-1% (P < 0.01), indicating continued and significant uptake of i-PTH at peritubular sites and a lesser role of glomerular filtration (GF) in the renal uptake of i-PTH. Since, under normal conditions, minimal i-PTH appears in the final urine, the contribution of GF and subsequent tubular reabsorption was further examined in isolated perfused dog kidneys before and after inhibition of tubular reabsorption by potassium cyanide. Urinary i-PTH per 100 ml GF rose from 8+/-4 ng/min (control) to 170+/-45 ng/min after potassium cyanide. Thus, i-PTH is normally filtered and reabsorbed by the tubular cells. The physiological role of these two mechanisms of renal PTH uptake was examined by giving single injections of b-PTH 1-84 or synthetic b-PTH 1-34 in the presence of established ureteral ligation. After injection of b-PTH 1-84, renal A-V i-PTH was 20% only while biologically active intact PTH was present (15-20 min). No peritubular uptake of carboxyl terminal PTH fragments was demonstrable. In contrast, after injection of synthetic b-PTH 1-34, renal extraction of N-terminal i-PTH after ureteral ligation (which was 13.4+/-0.6% vs. 19.6+/-0.9% in controls) continued for as long as i-PTH persisted in the circulation. These studies indicate that both GF and peritubular uptake are important mechanisms for renal PTH uptake. Renal uptake of carboxyl terminal fragments of PTH is dependent exclusively upon GF and tubular reabsorption, whereas peritubular uptake can only be demonstrated for biologically active b-PTH 1-84 and synthetic b-PTH 1-34.     

Serum proinsulin in normal and gestational diabetic pregnancy

The tubular transport of urate and sodium was examined by clearance, free-flow micropuncture, intratubular microinjection and precession techniques in control rats and in rats receiving a new uricosuric diuretic, indanyloxyacetic acid (MK-196). The i.v. infusion of MK-196 (50 mg/kg of body wt/hr) resulted in significant increases in the fractional excretion of sodium (FENa) from 0.98 +/- 0.01 to 11.86 +/- 2.88% (P less than 0.001) and in FEurate from 14.1 +/- 1.03 to 56.0 +/- 2.86% (P less than 0.001). End-proximal tubular fluid to plasma inulin (TF/Pinulin) ratios were 2.43 +/- 0.15 and 2.51 +/- 0.10 in control and drug-treated animals, respectively (P = NS). Total urinary urate recovery after MK-196 administration was higher following microinjections of [2-14C] urate into early proximal tubule sites: 70.5 +/- 2.7% in controls vs. 84.9 +/- 0.9 (P less than 0.001), and after microinjections into late proximal tubule sites: 82.8 +/- 2.9% vs. 91.3 +/- 1.9 (P less than 0.05). Urinary precession of urate from inulin was demonstrable following placement of isotopes of these compounds on the surface of the kidney in controls, but was abolished by MK-196. This agent, therefore, inhibits the reabsorption and secretion of urate in the proximal convoluted tubule, the net effect being a marked increase in urinary urate excretion. By contrast, its inhibitory effect on sodium reabsorption is exerted at a site or sites distal to the accessible portion of the proximal tubule. The demonstration of reduced urate reabsorption and normal sodium reabsorption in the proximal tubule suggests that the reabsorption of these constituents of the glomerular filtrate is not intimately linked at this nephron site.     

Public health developments in colonial Malaya: colonialism and the politics of prevention

-Previous studies have shown that whereas the nonclipped kidney in two-kidney, one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA, intrarenal angiotensin II (Ang II) levels are not suppressed; however, the distribution and functional consequences of intrarenal Ang II remain unclear. The present study was performed to assess the plasma, kidney, and proximal tubular fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g. Thus, as found in kidneys from normal rats with normal renin levels, proximal tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the confounding effects of decreases in mean arterial pressure (MAP), we administered the nonsurmountable AT1 receptor antagonist candesartan directly into the renal artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but effectively prevented the renal vasoconstriction elicited by an intra-arterial bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min-1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C hypertensive rats. These results show that proximal tubular fluid concentrations of Ang II are in the nanomolar range and are much higher than can be explained on the basis of plasma levels. Further, the data show that the intratubular levels of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in kidneys with normal renin content and could be exerting effects to suppress renal hemodynamic and glomerular function and to enhance tubular reabsorption rate.     

Nephrotoxicity of cyclosporine in humans: effect of cyclosporine on glomerular filtration and proximal tubular reabsorption

The chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (CIn) and PAH para-amino-hippuric acid (CPAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/CIn). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). CIn and CPAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/CIn was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.     

The effect of 1-alpha-hydroxycholecalciferol on the renal handling of phosphate in parathyroidectomized man

In a previous investigation by our group it was suggested that the stimulating effect of 1-alpha-hydroxycholecalciferol (1-alpha-OH-D3) on the tubular reabsorption of phosphate is mediated via the parallel suppression of the parathyroid hormone (PTH). A direct effect of 1-alpha-OH-D3 on the renal tubule could however not be completely excluded. Therefore, the effect of 1-alpha-OH-D3 was studied in 5 totally parathyroidectomized patients, in whom concomitant suppression of PTH would not occur. TmP/GFR, i.e. the ratio between the maximal tubular reabsorption of phosphate (TmP) and the glomerular filtration rate (GFR), was used as an indicator of the renal handling of phosphate. Estimation of TmP/GFR was performed 1) when the patients were vitamin D depleted and hypocalcemic, and 2) after 14-27 days of treatment with 1-alpha-OH-D3 to obtain stable normocalcemia. In patients with absent parathyroid function, no effect of 1-alpha-OH-D3 on TmP/GFR could be demonstrated. It is therefore concluded that 1-alpha-OH-D3 exhbits no antiphosphaturic effect in the absence of PTH and that the previously demonstrated antiphosphaturic effect of 1-alpha-OH-D3 in man is mediated via a concomitant suppression of PTH.     

Inhibition of proximal tubular hydrolysis and reabsorption of bradykinin by peptides

[3H] bradykinin ([3H] BKN) was microinfused alone or in the presence of a 390- or 780-fold excess of BKN or angiotensin I (AI) into proximal tubules in Inactin-anesthetized rats. Urinary excretion of 3H-labeled material was measured, and intact peptide and its metabolites were identified and quantified. When [3H] BKN was administered with BKN or AI, urinary recovery of 3H-labeled material was increased in a manner directly proportional to tubular length, suggesting that reabsorption of [3H] BKN is related to extent of tubular contact. BKN and AI were equally effective in inhibiting the reabosroption of [3H] BKN and its metabolites from proximal tubular fluid. In contrast, BKN but not AI effectively inhibited the enzymatic hydrolysis of [3H] BKN in the proximal tubule, The data suggest that the proximal tubular mechanism for reabsorbing BKN and its metabolites is of high capacity but not high specificity and that the mechanisms for enzymatic cleavage and reabsorption of BKN and its metabolites may had different specificites and capacities.     

The bumetanide-resistant part of forskolin-induced anion secretion in rat colon

The hemodynamic and urinary Na+ excretory response to a 2.5-fold increase in NaCl by i.v. infusion were assessed in conscious male rabbits with either high (BShi, salt-insensitive) or low (BSlo, salt-sensitive) cardiac baroreflex sensitivity, before, and 11-14 days after bilateral renal denervation. Effective renal plasma flow (ERPF) and proximal tubular Na+ reabsorption were measured by para-amino-hippurate (PAH) and Li+ clearances, respectively, before and after NaCl infused for 2 hr at a rate of 0.11 mL/kg/min. Intact BShi rabbits, showed a significant natriuresis within 30 min which was associated with an increase in ERPF and inhibition of proximal tubular reabsorption. The Na+ excretion rate was much slower in BSlo rabbits, while ERPF and proximal tubular reabsorption remained unchanged. Renal denervation reduced MAP, increased basal ERPF, Na+ and Li+ excretion in both groups, and abolished the difference in the renal hemodynamic re-sponse and Li+ excretion to increased NaCl, but not that in the rate of Na+ excretion. The data suggest that BSlo rabbits do not increase their ERPF and Li+ in response to saline because of an inability to bring about an inhibition of renal sympathetic nerve activity. This could be due to an impairment in the sensitivity of their cardiopulmonary baroreceptors. The difference in the rate of natriuresis in the two groups of rabbits which remained after renal denervation could involve an additional hormonal or a local renal mechanism.     

Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats

In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. 1965

The mechanism of HCO3- reabsorption in proximal and distal tubules was examined in rats undergoing NaHCO3 diuresis. The steady-state intratubular pH was measured with pH-sensitive glass microelectrodes and compared with the equilibrium pH calculated from the HCO3- concentration of the tubular fluid (measured with quinhydrone electrodes) and plasma Pco2. In the proximal tubule the intratubular pH and the equilibrium pH were identical, indicating no accumulation of excess H2CO3. After inhibition of carbonic anhydrase, however, intratubular pH was significantly lower (0.85 pH U) than the equilibrium pH. It was concluded that HCO3- reabsorption in the proximal tubule was mediated by H+ secretion, but that carbonic anhydrase located in the luminal membrane of the cell prevented H2CO3 from accumulating in the tubular fluid. In the distal tubule the intratubular pH was 0.85 U lower than the equilibrium pH. This difference could be obliterated by an intravenous injection of carbonic anhydrase. It was concluded that HCO3- reabsorption in this segment was also accomplished by H+ secretion. The accumulation of excess H2CO3 in the tubular fluid indicated that, in contrast to the proximal tubule, carbonic anhydrase was not located in the luminal membrane of distal tubular cells.     

Alpha 2-adrenoceptors determine the response to nitric oxide inhibition in the rat glomerulus and proximal tubule

Arginine-derived nitric oxide exerts control over the processes of glomerular filtration and tubular reabsorption. The tonic influence of nitric oxide over both of these is eliminated by renal denervation. The hypothesis that the renal nerves function, in this regard, via the activation of alpha 2-adrenoceptors was tested by renal micropuncture. The physical determinants of glomerular filtration and proximal tubular reabsorption were assessed in Munich-Wistar rats before and during the administration of the nitric oxide synthase inhibitor NG-monomethyl L-arginine (L-NMMA). In one set of studies, the systemic infusion of the alpha 2-agonist B-HT 933 rendered nephron GFR, nephron plasma flow, and proximal reabsorption sensitive to reduction by L-NMMA after renal denervation. In a second set of studies, the infusion of the alpha 2 receptor antagonist, yohimbine, to rats with renal nerves intact was found to suppress the effects of L-NMMA on nephron plasma flow and proximal reabsorption. The effects of L-NMMA on nephron GFR and nephron plasma flow, afferent and efferent arteriolar resistances, and proximal reabsorption correlated with the level of underlying alpha 2-adrenergic activity. The activation of renal alpha 2-adrenoceptors increases the influence of arginine-derived nitric oxide in the glomerulus and proximal tubule.     

Renal function and oxygen consumption during bacteraemia and endotoxaemia in rats

BACKGROUND: The hypothesis that renal failure during septic shock may occur as a result of hypoxia-related cell dysfunction was investigated in two rat models of distributive shock. METHODS: Pentobarbitone-anaesthetized rats received either a bolus (1 ml) of living Escherichia coli bacteria (hospital-acquired strain, 1 x 10(9) CFU/ml; BA-group, n = 7), or a 1-h infusion of endotoxin (E. coli O127.B8: 8 mg/kg; ET-group, n = 7), or saline to serve as time matched controls (C-group, n = 7). RESULTS: Urine flow in the BA- and ET-group reached a nadir at 1 h, but thereafter increased and reached values higher than control at 3 h. At this time point, renal oxygen delivery had decreased, in the BA-group mainly due to a fall in arterial oxygen content and in the ET-group to a fall in renal plasma flow (clearance of 131I-hippurate). However, renal oxygen extraction had significantly increased, by 31% in the BA and by 59% in the ET group, while renal oxygen consumption remained the same. Net tubular sodium reabsorption had decreased by 55% in the BA and by 25% in the ET group, due to a fall in glomerular filtration rate (clearance of creatinine). Hence, an excess oxygen consumption was found which was caused neither by an increased renal glucose release nor by the presence of an increased number of leukocytes stuck in the glomeruli. Renal tubular cells showed normal morphology. An indication that proximal tubular function in the BA and ET group remained largely intact were normal ATP levels, absence of urinary glucose, and a normal fractional excretion of sodium. However, since urine flow had increased in shocked rats at 3 h, water appeared selectively lost. CONCLUSIONS: Our data indicate that in rat models of septic shock renal failure is not caused by cortical hypoxia or a shortage of cellular energy supply.     

Estrogen effects on the renal handling of calcium in the ovariectomized perfused rat

Estrogen deficiency is a major cause of bone loss in women but the mechanism is unclear. The ovariectomized (OVX) rat is a well recognized model for post-menopausal osteoporosis. In this study we have examined the effects of OVX and estrogen replacement in the OVX rat on the renal handling of calcium in response to alterations in the calcium load in the perfused rat. The interaction of estrogen administration and parathyroid hormone (PTH) was also examined in the OVX, parathyroidectomized (PTX) rat. Calcium or EDTA was infused into sham or OVX rats to obtain a range of filtered calcium loads. The excretion of calcium, was compared to the filtered load for the data from both perfusions indicating a lower calcium (P = 0.006) and sodium (P = 0.009) excretion in the OVX rat. A similar result was seen in the OVX rat replaced with 20 micrograms of estrogen valerate 48 and 24 hours prior to perfusion with calcium excretion being greater with estrogen administration (P = 0.005) compared to vehicle alone. This was not observed in the parathyroidectomized rat. Correlations between sodium and water reabsorption and calcium and sodium reabsorption during perfusion indicate that the results of OVX were due primarily to proximal tubule effects. Prior to the perfusion experiment PTH (sham vs. OVX pmol/liter, mean +/- SD; 20 +/- 6 vs. 18 +/- 4) and calcitriol (128 +/- 85 vs. 97 +/- 74) were similar in both groups, indicating that the results were not dependent on calcitropic hormone effects. It is concluded that, in the perfused rat, OVX results in decreased excretion of calcium and sodium as a result of estrogen effects on the renal proximal tubule, an effect dependent on PTH. This effect is opposite to that found in postmenopausal women, perhaps due to the high filtered load of calcium used in the experimental design and species differences in the relative importance of proximal versus distal calcium handling.     

Effect of substance P on proximal tubular reabsorption in the rat

Micropuncture and clearance techniques were used simultaneously to determine the effect of substance P on proximal tubular and overall renal function in anesthetized rats. This polypeptide, infused in saline at 50 pg/min into the abdominal aorta above the renal arteries, produced increases in urine flow, 2.7-3.7 mul/min.g kidney wt (P is less than 0.005); urinary sodium concentration, 32-61 meq/liter (P is less than 0.01); and sodium excretion, 89-223 neq/min (P is less than 0.005). Tubular fluid to plasma inulin concentration ratio measured in the last accessible proximal convolution fell from 2.21 to 1.80 (P is less than 0.001), and thus fractional reabsorption was reduced from 54 to 44% (P is less than 0.001). Absolute reabsorption by the proximal convoluted tubule was also reduced 15.5-12.5 nl/min (P is less than 0.025). In a control series of animals, saline alone infused at the same rate did not produce any statistically significant changes in the measured parameters over the same time period. The intrerenal mechanism responsible for the reduction in proximal reabsorption appears to be a tubular one since no consistent or significant changes were observed in kidney or single nephron glomerular filtration rate, renal plasma flow, or intrarenal hydrostatic pressures. No evidence was found to indicate redistribution of filtration rate, or plasma flow, or a reduction in filtration fraction.     

Oxytocin and renal function in the rat; an investigation of a possible proximal site of action

Direct measurements of proximal tubular fluid reabsorption have been employed to examine the possible renal site of action of oxytocin. In whole kidney studies the natriuresis and chloriuresis, which occurred during the period of oxytocin infusion, did not coincide with the associated diuresis. The latter reached a peak 10-20 min after hormone administration has ceased. The separation in the saliuretic and diuretic responses underlines the apparent independence of these actions of oxytocin on the renal handling of water and electrolytes. The disturbances in renal function were not related to any change in glomerular filtration rate (gfr) and an examination of single nephron function failed to detect any significant effect of oxytocin on proximal tubular reabsorption. The renal actions of oxytocin would therefore appear to emanate from altered tubular rather than glomerular function, though the present study provides no support for a proximal site of action.     

Cardiorespiratory and renal responses to arterial chemoreceptor stimulation by hypoxia or almitrine in men

1. The cardiorespiratory and renal responses to 3 h of normobaric whole-body hypoxic hypoxia (FiO2 = 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls. 2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole-body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration-fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant. 3. Renal fractional lithium excretion decreased significantly in response to whole-body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes. 4. The data indicate that, in humans, both almitrine and whole-body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics. 5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well-tolerated, whole-body hypoxic hypoxia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.     

Renal excretion of urate in mongrel and Dalmatian dogs: a micropuncture study

Free-low micropunction experiments were performed in mongrel dogs and in Dalmatian coach hounds infused with urate to obtain Purate levels of 0.15-0.21 mM before and during the infusion of pyrazinioc acid (PZA). In the absence of PZA, mongrel dogs excreted approximately 50% and Dalmatians 140% of filtered loads of urate. In mongrel dogs net reabsorption occurred only in the proximal convoluted tubules. PZA enhanced net proximal reabsorption and revealed the occurrence of proximal secretion, whereas fractional urate excretion in the urine decreased only slightly. In Dalmation dogs urate fluxes across walls of proximal convoluted tubules resulted in either net reabsorption or net secretion, with no mean change. Net urate secretion occurred between superficial late-proximal and early-distal tubules, and considerably decreased fractional excretion of urate. The renal handling of PZA was similar in mongrel and in Dalmatian dogs.