Hepatic portal vein infusion of glucose on sodium excretion in the rat.

Anesthetized rats were prepared with catheters in the hepatic portal (HPV) and femoral (FEM) veins and in the bladder or ureters. In some experiments the left kidney was denervated. HPV infusion of 1 M glucose at 2 ml/h for 20 min increased Na excretion by the kidney when given as a second infusion. Bilateral cervical vagotomy eliminated the increase in Na excretion during glucose infusion and uncovered a delayed decrease in Na and K excretion. Renal denervation attenuated the increase in Na excretion to HPV glucose. FEM infusion of glucose had variable effects, increasing Na excretion only after vagotomy. The results are interpreted to suggest that central and vagal receptors tend to enhance Na excretionwhereas splanchnic nerve afferents and humoral mediator(s) have the opposite effect.     

Water and sodium excretion in unilaterally denervated normal and sodium depleted anesthetized rats before and after plasma volume repletion

The possible role of a reduction in plasma volume (PV) by surgery as well as the importance of dietary Na supply in denervation natriuresis have been investigated on Inactinanesthetized male rats subjected to acute unilateral renal sympathectomy. Four groups were studied: I. Normal Na diet (n=14); II. Low Na diet (boiled rice for 2 weeks)-isotonic glucose infusion (n=10); III. Low Na diet-isotonic saline infusion (n=5); IV. Normal and low Na diet rats served as conscious control (n=10). Surgery caused a 9–11% increase in hematocrit and a 15–18% decrease in PV in groups I–III. Plasma volume repletion (PVR) reverted these changes. In group I sodium excretion from both kidneys was only a fraction of that in conscious animals kept on the same diet (group IV) and marked denervation natriuresis was observed. After PVR sodium output of innervated (I) kidneys was not different from that of conscious rats but denervated (D) kidneys excreted twice that amount. In group II Na excretion was increased compared to conscious Na depleted controls, and PVR augmented further this difference. Surprisingly, the difference in urinary sodium excretion (U_NaV) between I and D kidneys was absent after surgery and was minimal after PVR in this group. In group III physiological saline infusion reverted the effect of Na depletion and denervation natriuresis was present both before and after PVR. It is concluded that PV reduction does not play a major role in denervation phenomenon. In Na depleted anesthetized rats denervation natriuresis is absent or minimal.     

Renal nerve blunts natriuretic and diuretic response to atrial natriuretic peptide in conscious rabbits

The contribution of the renal nerve to the natriuretic and diuretic responses to rat atrial natriuretic peptide (rAMP) was investigated in conscious rabbits with unilateral renal denervation. Renal nerve activity (RNA) was measured at the contralateral innervated kidney. Catheters were bilaterally implanted into the ureters. Urine samples were collected from each kidney by gravity drainage at 10-min clearance intervals. In rabbits with all baroreflexes intact, infusion of rANP at 0.3 micrograms/(kg.min) for 30 min decreased mean arterial pressure by 8 +/- 4 mmHg and increased RNA by 53 +/- 13%. After sinoaortic baroreceptor denervation (SAD), hypotensive response to infusion of rANP was greater than that in intact rabbits, while RNA did not change. After SAD plus vagotomy, infusion of rANP lowered mean arterial pressure by 21 +/- 4 mmHg and RNA by 19 +/- 6%. In the denervated kidney, infusion of rANP increased Na+ excretion by 16.1 +/- 4.5 from 3.5 +/- 1.0 muEq/min and water excretion by 0.17 +/- 0.05 from 0.08 +/- 0.02 ml/min. In the contralateral innervated kidney, infusion of rANP increased the amount of Na+ and water excretion by 4.5 +/- 3.2 muEq/min and 0.07 +/- 0.04 ml/min, which were significantly less than those in the denervated kidney. These results indicate that infusion of rANP increases RNA, due to baroreceptor reflexes, and that this increase in RNA blunts natriuretic and diuretic action of rANP.     

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Infusions (20 μl/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65 and 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 h dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a value below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion without causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.     

Stimulation of tubular reabsorption of magnesium and calcium by antidiuretic hormone in conscious rats

The effect of antidiuretic hormone on urinary electrolyte excretion was investigated by clearance techniques in conscious rats in metabolic cages. Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) were studied in the absence of exogenous ADH (control group = C,n=4), and after several weeks of continuous dDAVP infusion (period A) followed by discontinuation of dDAVP (period B) (experimental group = E,n=6). dDAVP, a non-pressor antidiuretic analogue to ADH, induced 1) a high urine concentration (2,645±44 (SEM) in group E vs 131±6 mosmol/kg H₂O in group C),P<0.001; 2) no significant change in plasma osmolality (288±2 vs 297±7 mosmol/kg H₂O respectively) and in plasma concentration of major electrolytes, Na, K, Cl, Mg, and Ca; 3) a large decrease in urinary excretion of calcium and magnesium and no change in other electrolyte or total osmolar excretion. Fractional excretions in rats of groups C and E during period A were, respectively, for Na: 0.59±0.03 (SEM) and 0.51±0.33% (NS), for Ca: 2.92±0.62 and 0.34±0.05% (P<0.001) and for Mg: 7.75±0.83 and 1.38±0.28% (P<0.001). After treatment discontinuation, plasma osmolality in group E rose to 304±2 mosmol/kg H₂O (P<0.01 compared to period A) with slight increases in plasma Na and Cl concentrations. Urine osmolality fell below, and urine flow rate rose above values observed in the control group. Fractional excretion of Ca and Mg rose to values seen in DI rats (3.30±0.37%, NS, for Ca) or above (26.95±0.65%,P<0.001, for Mg), with no change in other solute fractional excretion. Other works, from our and other's groups have shown that 1) long-term exposure to dDAVP induces a marked hypertrophy of the epithelium of the thick ascending limb of Henle's loop in its medullary part (MTAL) and 2) dDAVP induces an increase in Ca and Mg tubular reabsorption between end proximal and early distal sites of micropuncture. Taken together, these results suggest that the effects of ADH on divalent cation fractional excretion, seen in the present study, probably results from an increased Ca and Mg voltage-dependent reabsorption in the MTAL. This reabsorption is linked to the increased salt transport induced in this segment, both by a direct effect of ADH and by an indirect effect resulting from the increased solute delivery to the MTAL in the concentrating kidney.     

Micropuncture studies of the renal effects of atrial natriuretic substance

Micropuncture studies of the renal effects of atrial natriuretic substance. Injection of atrial extract produced by homogenization, boiling and centrifugation of atrial tissue from one heart caused a 10 fold increase in urine flow rate and a 30-fold increase in Na excretion. Similarly prepared extracts of ventricle were without effect. To identify the site of action of atrial natriuretic substance, extract was infused intravenously at rates corresponding to 3 or 6 atria per hour. During infusion at a rate of 3 atria per hour mean urine flow increased from 9.5±2.8 to 17.2±1.2 l/min and Na excretion from 0.14±0.06 to 1.78±0.14 mol/min. Glomerular filtration rate (GFR), single nephron filtration rate (SNGFR) and proximal and loop of Henle fluid absorption did not change significantly. During infusion of 6 atria per hour, paralleling a greater rise in urine flow rate (from 6.4±2.09 to 40.3±7.5 l/min) and in sodium excretion (from 0.18±0.0008 to 5.97±0.93 mol/min), filtration rate, measured for either the single nephron or the whole kidney, rose. As a consequence of the rise in GFR, delivery of fluid and chloride into the distal tubule increased significantly. These data suggest that to a major extent the natriuresis is caused by transport inhibition along collecting tubules and collecting ducts. In addition, at high doses a rise in filtration rate contributes to the natriuretic effect of atrial extracts.     

Effect of insulin and prednisolone on transport of organic substances in the dog kidney

In experiments on dogs a single injection of insulin in a dose of 1 unit/kg body weight caused an increase in the maximal reabsorption of glucose and secretion of diodone and reduced the excretion of sodium without any change in glomerular filtration. These effects depend on the direct action of insulin, for when it was injected directly into one of the renal arteries its action was manifested only in the kidney on the side of infusion. Prednisolone had no significant effect on glucose and diodone transport when given as a single injection (3–4 mg/kg) or over a period of 10 days (1.5–2 mg/kg daily).Department of Pharmacology, Altai Medical Institute, Barnaul. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 694–697, December, 1978.     

Effect of saline infusion on net reabsorption of endogenous sulfate relative to that of phosphate in intact and thyroparathyroidectomized rats

Clearance experiments have been performed to study the effects of saline infusion on the reabsorption of inorganic sulfate (SO₄) at endogenous levels. Adult female Sprague-Dawley rats on a standard diet were used. Both intact and thyroparathyroidectomized (TPTX) animals were infused with a 130 mmol/l sodium chloride solution at a low (0.15 ml/min) and a high (0.375 ml/min) rate. This increase of the infusion rate decreased the reabsorption of SO₄ in both groups of animals significantly. The fractional excretion of SO₄ in theintact rats increased from 9.9±5.6 to 18.4±3.6% (mean values±SD,p<0.001) and in theTPTX rats from 5.3±2.5 to 22.4±6.3% (p<0.001). It is concluded that endogenous parathyroid hormone has no major effect on the saline-induced inhibition of reabsorption of SO₄.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Fr 239/9-1)     

Endogenous opioids and electrolyte excretion after contralateral renal exclusion

Acute reductions in functioning renal mass result in increases in both sodium (U Na V) and potassium (U K V) excretion by the contralateral kidney (CK). We studied the role of endogenous opioids in this response. In control experiments acute unilateral nephrectomy (AUN) increased U Na V from 1,788 +/- 1,125 (SD) to 3,939 +/- 1,819 and U K V from 1,385 +/- 561 to 2,254 +/- 832 neq/min by the CK (P less than 0.005 for both); similar results occurred in rats undergoing acute unilateral ureteral occlusion (UUO). These increases occurred without overall change in GFR or mean arterial pressure. In rats receiving a continuous infusion of the opiate-receptor antagonist naloxone (0.3 mg . kg-1 . h-1) neither AUN nor UUO produced significant alterations in U Na V or U K V by the CK; naloxone infusion by itself did not alter GFR or basal rates of cation excretion. A separate group of rats was made tolerant to morphine by subcutaneous implantation of pellets containing 75 mg morphine base. In these rats, AUN also failed to produce any increase in U Na V or U K V by the CK. The results suggest that acute reductions in functioning renal mass produced by either AUN or UUO stimulate cation excretion by the remaining kidney through reflex pathways that involve opiate receptors.     

Reducing brain sodium concentration prevents post-prandial and dehydration-induced natriuresis in sheep

Renal Na excretion during the 24 h following feeding was studied in sheep. A pronounced natriuresis occured 3.5-5.5 h after feeding. Na excretion then fell to low levels in animals allowed to drink water, but was significantly elevated above this level in water-deprived sheep for most of the remaining period. Both the post-prandial and dehydration-induced natriuresis were prevented by intracerebroventricular (icv) infusions of low Na concentration 0.3 mol 1^-1 mannitol at 1 ml h^_1, and a water diuresis also occurred. These effects were not caused by icv infusion of artificial cerebrospinal fluid (Na concentration = 150 mmol l^-1). As a result, there was a much greater increase in plasma Na concentration and osmolality in the sheep given icv mannitol. Intravenous infusion of vasopressin prevented the water diuresis induced by icv mannitol, but the inhibition of natriuresis was still observed and plasma Na concentration increased by 8 mmol l^-1 over 24 h compared with an increase of 3 mmol l^-1 in dehydrated sheep infused icv with artificial cerebrospinal fluid. The results show that the ambient Na concentration in the brain plays an important role in the normal homeostatic regulation of Na balance by the kidney in sheep.     

The effect of prostaglandin inhibition on renal function in the developing anesthetized lamb

The importance of prostaglandin (PG) compounds for renal function in the developing kidney was studied by comparing renal blood flow (RBF), glomerular filtration rate (GFR) and fractional sodium (Na) excretion in control lambs and lambs treated with a PG synthesis inhibitor, indomethacin. The lambs were 1–2 and 4–6 weeks old and they were studied either during hydropenia (HP) or volume expansion (VE). lndomethacin significantly decreased Na excretion in both groups of hydropenic lambs. lndomethacin also completely blunted the natriuretic response to VE in the older lambs but had no effect on Na excretion in the volume expanded younger lambs. It is concluded that partial lack of PG inhibiting action on tubular Na transport will contribute to the poor natriuretic response to VE in neonatal lambs. Since PG will act locally rather than being blood-borne messengers, the divergent PG action in younger and older lambs might be explained by local differences in maturation of PG metabolism as well as by local differences ir the maturation of PG sensitivity.     

Effect of splanchnicotomy on the renal excretion ofd-glucose in the anaesthetized dog

Summary The effects of acute intravenousd-glucose (G) loading were studied on anaesthetized, unilaterally splanchnicotomized (renal denervation) dogs. Glomerular filtration rate (GFR) was generally not different on the innervated and denervated side, while urine flow (V), sodium excretion (U_NaV) and urinary excretion (U_GV) of glucose on the splanchnicotomized side were significantly increased at any plasma G concentration. Tubular reabsorption (T_G) as well as Tm of G in denervated kidneys was considerably depressed. In a series of experiments with moderately elevated plasma glucose level glucosuria on the sympathectomized side was found that seems to be the consequence of a lower threshold for G in denervated kidneys. The positive correlation between the tubular reabsorption of Na and G was not influenced by renal denervation.     

Supersensitivity of the renal tubule to catecholamines in the chronically denervated canine kidney

Experiments were performed on anesthetized dogs to study whether or not renal tubules of the chronically denervated kidney show supersensitivity toward circulating catecholamines. In one kidney the influence of plasma catecholamines was inhibited by intrarenal administration of the alpha adrenergic receptor blocker phenoxybenzamine (POB, 2 g/min), and renal parameters of the infused kidney were compared to those of the contralateral noninfused organ. Before POB infusion urine flow (V), urinary sodium and potassium excretion (U_NaV, U_KV) as well as clearance of inulin and PAH (GFR, C_PAH) were similar in infused and contralateral kidneys in all the groups studied. In dogs (n=8) with two innervated kidneys POB infusion elevated V and U_NaV by 53±13% and 102±34% (p<0.05). In dogs (n=8) with acute bilateral renal denervation POB administration failed to alter any of the measured parameters. In contrast, V and U_NaV from chronically denervated kidneys (n=7) were increased after POB infusion by 40±9% and 103±34% (p<0.05). Glomerular filtration rate, C_PAH and U_KV were not changed by alpha adrenoceptor blockade in any of the groups. In an additional group of animals (n=8) acute unilateral renal denervation increased V and U_NaV to a significantly higher extent (by 282±85% and 330±106%) than POB administration did in the innervated kidney and elevated U_KV (44±10%), too. It is concluded that supersensitivity to catecholamines developed in renal tubules of the chronically denervated dog kidney and, in consequence, circulating catecholamines at elevated plasma levels caused by surgery were capable of increasing tubular reabsorption of sodium and water.     

Relationship between glucose and sodium excretion in the new-born dog

1. The relationship between renal glucose and sodium excretion was studied in thirty-three new-born dogs aged 1-14 days and in ten adult dogs.2. Glucose was infused into the animals at rates sufficient to produce an amount of filtered glucose at least 1.5 times the tubular transport of glucose (saturating glucose load). In both puppies and adults tubular glucose reabsorption at saturating glucose loads varied directly with the glomerular filtration rate (r = 0.54 and 0.73 respectively, P < 0.01 for both).3. In the puppy, as the fraction of filtered sodium excreted (C(Na)/C(In)) increased from 0.05 to 0.45, the ratio, renal tubular glucose transport divided by glomerular filtration rate at saturating glucose loads, (T(G)/GFR)(m), decreased from 3.7 to 1.7 mg/ml. (r = -0.75, P < 0.01). In the adult C(Na)/C(In) was below 0.08 in all experiments and (T(G)/GFR)(m) was within the 95% confidence limits predicted by regression analysis of the data from puppies. Although mean (T(G)/GFR)(m) was greater in the adult than in the puppy (P < 0.01), when puppies had C(Na)/C(In) similar to that for adults, they had (T(G)/GFR)(m) values equivalent to that for the adult.4. There was excellent correlation between glucose excretion and water excretion for both adult and new-born dogs (r = 0.93 and 0.87, respectively). However, for any glucose loss, water loss was greater in the puppy than in the adult (P < 0.01).5. During the control period total sodium excretion (per gram kidney) and C(Na)/C(In) were similar in the new-born and adult dog. However, during glucose loading, the puppies excreted more sodium and had a higher C(Na)/C(In) than did the adult, although glucose excretion was greater in the adult than in the puppy (P < 0.01 for all comparisons).6. Glomerular blood flow, as measured by radioactive microspheres, was redistributed towards inner cortical nephrons during glucose loading in the puppy. There was no such redistribution of glomerular blood flow in the adult.7. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. In the puppy, the increase of C(Na)/C(In) following a glucose load was the same whether the glucose load followed control or distal blockade collections, suggesting that reductions of sodium reabsorption following a glucose load probably came from the proximal tubule. C(Na)/C(In) during glucose loading plus distal blockade was significantly (P < 0.01) higher in the puppy (0.598) than in the adult (0.280), indicating that glucose diuresis produced a greater inhibition of proximal tubular sodium reabsorption in the new-born than in the adult dog.These results support the hypothesis that the high sodium excretion rate during glucose diuresis in the new-born dogs appears to be due to the greater sensitivity of the neonatal proximal tubule to the osmotic effect of glucose. When presented with a glucose osmotic load the new-born dog diminishes net proximal sodium reabsorption more than does the adult and thus depresses tubular glucose reabsorption to a greater extent. The lower values of maximal glucose transport rates found in new-born animals may be related, therefore, to the higher fractional sodium excretion rates during glucose diuresis rather than to a diminished intrinsic glucose transport capacity in the new-born kidney.     

Inhibition of vasopressin-release during developing hypernatremia and plasma hyperosmolality: an effect of intracerebroventricular glycerol

In non-hydrated goats prolonged (3 h, 0.02 ml/min) intracerebroventricular (IVT) infusion of 0.35 M glycerol depressed the plasma vasopressin level during the entire infusion period which resulted in a conspicuous water diuresis outlasting the infusion by about 20 min. Since no compensatory drinking occurred during this sustained water diuresis it gradually induced pronounced dehydration (loss of greater than 1 liter of total body water causing 5% increase in plasma [Na+] and osmolality). The same degree of dehydration was in other experiments induced by water deprivation. It then caused a 5-fold increase in plasma vasopressin level. Corresponding IVT infusions of 0.35 M d-glucose depressed plasma vasopressin level only during the first half of the 3 h infusion period. Consequently, the resulting water diuresis was transient and subsided before the glucose infusion was finished. Plasma renin activity increased during the IVT glycerol infusion and during water deprivation, but was largely unaffected by IVT glucose. Both IVT glycerol and glucose decreased renal sodium excretion. The possibility is discussed that the pronounced ability of IVT glycerol to depress the vasopressin release and thirst is not only due to dilution induced reduction of CSF [Na+], but also to an influence of glycerol on choroidal and/or transependymal Na+-transporting mechanisms.     

Effect of Na−K-ATPase inhibition on hydrogen ion and potassium secretion

The purpose of the present study was to examine whether in vivo inhibition of renal Na–K-ATPase affects renal H⁺ and potassium (K) secretion. Infusion of digoxin, furosemide, or ethacrynic acid into one renal artery of HCO₃ loaded dogs caused similar increases in urine flow, fractional Na and Cl excretion, and fractional water excretion. Glomerular filtration rate and urinary HCO₃ concentration fell comparably in all experiments. Maximal HCO₃ reabsorption was not depressed by any of the drugs infused, however only digoxin inhibited renal Na–K-ATPase activity. Furthermore, unilateral digoxin infusion resulted in a marked depression in the urine to bloodpCO₂ gradient (U-BpCO₂) and prevented the rise in fractional K excretion secondary to HCO₃ infusion observed in the contralateral control kidney. At all urinary HCO₃ concentrations, U-BpCO₂ was significantly higher in urine obtained from furosemide or ethacrynic acid infused kidneys than in urine obtained from digoxin infused kidneys. In addition, furosemide or ethacrynic acid administration markedly enhanced fractional K excretion in both kidneys. The systemic infusion of tris(hydroxymethyl)aminomethane (THAM; pK 8.0) failed to return U-BpCO₂ in the digoxin infused experimental kidneys to control levels, whereas THAM caused a marked rise in U-BpCO₂ in the control kidney. These data demonstrate that the in vivo inhibition of renal Na–K-ATPase by digoxin causes a defect in the secretion of both H⁺ and K. This defect likely results from the dissipation of the Na dependent lumen negative potential difference (PD) by digoxin, since a lumen negative PD favors both H⁺ and K secretion in the collecting duct. Furthermore, these data do not support the notion that furosemide or ethacrynic acid affect tubular transport through the inhibition of renal Na–K-ATPase activity.     

The functional state of the isolated rabbit kidney perfused with autologous blood

This report describes the technique and procedure for perfusing an isolated rabbit kidney with 25 ml heparinized autologous blood in a closed circuit including a pump and an oxygenator. The duration of the operative ischaemia was 5-8 min; the perfusion lasted 2.5 hours. An additional infusion was made to compensate for urinary losses. Renal blood flow increased progressively from 2.01+/-0.1 to 2.65+/-0.22* ml/g kidney weight (kw) per min (*P<0.05). Between the first (P1) and the last (P4) urine collection period the glomerular filtration rate (GFR) fell from 288+/-25 to 217+/-38* microl/g kw per min, urine flow from 5.58+/-1.13 to 4.91+/-0.75 microl/g kw per min, Na+ excretion from 1.07+/-0.19 to 0.63+/-0.12* micromol/g kw per min, K+ excretion from 0.46+/-0.03 to 0.28+/-0.05* micromol/g kw per min, P excretion from 2.5+/-0.2 to 2.0+/-0.5 microg/g kw per min, Ca excretion from 0.4+/-0.1 to 0.12+/-0.05* microg/g kw per min, creatinine excretion from 6.94+/-0.32 to 5.68+/-0.54 microg/g kw per min, glucose excretion from 18.2+/-3.2 to 1.6+/-0.5* microg/g kw per min, the free water clearance (CH2O) from -6.57+/-0.85 to -5.10+/-1.31 microl/g kw per min and urine osmolality from 600+/-52 to 590+/-105 mOsm/kg, urea excretion from 0.75+/-0.16 to 0.95+/-0.13 micromol/g kw per min. Excretion of glucose, P or Ca was observed only above a given plasma threshold value, and no transport maximum was found for glucose or P. Ca reabsorption paralleled the Na reabsorption. The proximal tubule pressure, measured within the 1st h of perfusion, was 12.5+/-1.1 mm Hg. Histological examination at the end of the perfusion showed dilatation of the tubules as in the non-perfused kidneys, and the presence of numerous bacteria. Hypertonic urine (380-1110 mOsm/kg) was observed in the presence of vasopressin, in the latter's absence the urine was hypotonic urine (206-278 mOsm/kg). There was no correlation between renal plasma flow and the GFR. CH2O increased with increasing filtered Na+ load. In conclusion, the blood-perfused, isolated rabbit kidney has a fairly constant functional capacity for approximately 2 h.     

Phosphate and cyclic AMP excretion decreases during less than 12 hours of hypoxia in conscious rats

Hypocapnia is known to have an antiphosphaturic effect that overcomes the phosphaturic effect of hypoxia. The objective of this study was to examine whether conscious rats exposed to acute hypoxia show a decrease in phosphate excretion due to the concomitant hypocapnia. Wistar rats weighing 200 g were exposed to hypoxia (inspired oxygen fraction=0.10) or normoxia (inspired oxygen fraction=0.21) for 6 h; and rats were alternately exposed to hypoxia or normoxia every 12 h for a total 36 h. Renal clearance and hormone studies were performed. Rats exposed to 6 h of hypoxia (n = 11) showed significant hypophosphaturia and decreases in absolute and fractional excretion of phosphate (0.38±0.10 μg min^-1, mean ±SE, P<0.0001 and 0.59±0.15%, P<0.0001) as compared with normoxic rats (n = 11, 3.91±0.68 μg min-¹ and 5.62±0.85%). In addition, nephrogenous adenosine 3′,5′-cyclic monophosphate level per glomerular filtrate was significantly decreased (-0.87±0.64 nmol dL GF^-1, P<0.05) and plasma parathyroid hormone level was unchanged (45.2±9.5 pg mL-¹) after 6 h of hypoxia as compared with normoxic rats (4.03±1.83 nmol dL GF-¹ and 54.3±10.4 pg mL-¹). A parallel increase in urinary noradrenaline and a decrease in dopamine excretion was observed in rats after 6 h of hypoxia. The decreased phosphate and adenosine 3′,5′-cyclic monophosphate excretion during acute hypoxia were restored to normoxic levels by reoxygenation with 21% oxygen in the study of 12-h intermittent hypoxia. In summary, (1) hypoxia produced by inhalation of 10% oxygen for 12 h or less causes reduced phosphate and adenosine 3′,5′-cyclic monophosphate (cAMP) excretion by spontaneously breathing rats; (2) these effects are reversed by reoxygenation and (3) hypoxia elicits a parallel increase in noradrenaline excretion and a decrease in dopamine excretion. These data suggest that renal adrenergic and dopaminergic systems play important roles in hypophosphaturia during acute hypoxia in conscious rats.     

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

Alterations in histamine metabolism of rat gastric mucosa following vagotomy

1. In female rats subjected to truncal vagotomy with pyloroplasty, pyloroplasty alone or sham operation, the behaviour of gastric mucosal histamine was investigated combining in vivo and in vitro methods.2. Following truncal vagotomy with pyloroplasty mucosal histamine formation, determined in vitro, increased about fivefold and histamine content was significantly elevated. The heightened histamine formation was reflected in increased excretion of histamine in the urine.3. On pentagastrin infusion, mucosal histamine formation increased about twofold following vagotomy with pyloroplasty and sevenfold in the sham-operated controls. Histamine content concomitantly fell in both groups to about the same level. These alterations were paralleled by increased excretion of histamine in the urine.4. Kinetic studies in which [(14)C]histidine was injected and the resulting urinary [(14)C]histamine determined, indicated that during the first hour of pentagastrin infusion newly formed histamine was more slowly mobilized following vagotomy with pyloroplasty than in the controls.5. In rats subjected to a pyloroplasty alone, the increase in urinary histamine on pentagastrin infusion was significantly larger than in the sham-operated controls. Kinetic studies indicated that this was due to a larger mobilization of preformed histamine.6. The changes in mucosal histamine metabolism are discussed in relation to the pattern of acid secretion following the actual surgical procedures.