bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal sodium reabsorption during saline loading and distal blockade in newborn dogs
Authors: Kleinman LI
Published: December 2017

The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.
Cardiorenal effects of lidocaine and procaine amide in the conscious dog
Authors: Mandel WJ , Laks MM , Arieff AI , Obayashi K , Hayakawa H , McCullen A
Published: December 2017

Simultaneous measurements of hemodynamics, arterioventricular (AV) conduction, and renal functioner were obtained in conscious dogs. Catheters were implanted for the long-term measurement of central aortic, right ventricular, and pulmonary artery pressure. AV conduction was assessed following surgical implantation of multipolar electrode plaques in the area of the bundle of His, as well as on the epicardium of the right and left atria and ventricles. Renal function was assessed utilizing standard techniques. Following control measurements, lidocaine, 1 mg/kg, or procaine amide, 10 mg/kg, was administered intravenously. Subsequently, serial measurements were obtained for a 90-min period. No significant changes in hemodynamics were observed following either drug. Procaine amide produced a significant increase in heart rate and a minimal increase in QRS duration associated with a decrease in low right atrial to His bundle conduction time. However, no significant changes in cardiac conduction were observed after lidocaine administration. Renal function was unaffected by lidocaine but significantly depressed by procaine amide, as demonstrated by a decrease in GFR and effective renal flow. In summary, acute administration of procaine amide significantly alters renal function in the conscious dog with minimal effects on AV conduction and hemodynamics.
Factors affecting thermogenic drinking in rats
Authors: Nelson EL , Fregly MJ , Tyler PE
Published: December 2017

After as little as 6 h of exposure to cold air, drinking was induced in rats following transfer from air at 5 degreesC to air at 26 degreesC. Drinking began within 15 min after transfer from the cold enviroment and lasted approximately 1 h. The stimulus for initiation of drinking was most likely the temperature change resulting from the transfer, since an ambient temperature difference of 10 centigrade degrees or more was required to initiate a drinking response after transfer from air at 5 degreesC.Thermogenic drinking was not thwarted by preventing access to water for either 1 or 2h following transfer to warm air, but either intragastric or intraperitoneal administration of a water load equal to 3% of body weight inhibited water intake following transfer.The characteristics of the drinking response following transfer than 5 to 26 degrees C were similiar to those observed following 24 h of dehydration at 26 degrees C. Thus, the cold-exposed rat is relatively dehydrated compared with controls.
Studies of the electrical potential difference in rat proximal tubule
Authors: Seely JF , Chirito E
Published: December 2017

The electrical potential difference (PD) in the rat proximal convoluted tubule was investigated in vivo as a function of distance from the glomerulus. The PD was found to be invariably negative (up to -4.5 mV) in the earliest segments (less than 0.5 mm from the glomerulus) and rose to positive values (+2 to +4) in the later segments (1 mm beyond the glomerulus). This change in PD correlated with the bubule fluid-to-plasma (TF/P) chloride ratios, which rose from unity in the early segments to approximately 1.3 in the late. Corresponding changes in PD and chloride ratios could be elicited by single-nephron stop-flow techniques in the early segments. Luminal perfusion techniques demonstrated a direct relationship between PD and tubule fluid chloride concentration. Acetazolamide was found to significantly reduce both late proximal PD (less than +2 mV) and TF/P chloride ratios (less than 1.06). Split-drop studies demonstrated that the negative PD in the early proximal tubule was dependent on the presence of glucose and alanine and the absence of a chloride gradient, whereas in the late proximal tubule under the same conditions the PD was not significantly different from zero. In this segment of the nephron the positive PD in free flow appeared to result from the chloride diffusion potential generated by preferential HCO3 reabsorption. These results provide further demonstration of intrinsic differences in the transport properties along the length of the proximal convoluted tubule.
Hemodynamics and blood flow distribution following prolonged circulation at 5 degrees C
Authors: Zarins CK , Skinner DB
Published: December 2017

Circulation was maintained in profoundly hypothermic dogs for 8 h at temperatures below 10 degrees C. During cooling to 5 degrees C cardiac output and blood pressure decreased and peripheral resistance rose. Thereafter, circulatory dynamics remained relatively stable over the next 6 h with a gradual decline in blood pressure. The proportion of blood flow to the heart and brain increased with cooling and remained elevated throughout the hypothermia period. Despite continued circulation, pulmonary edema developed after 5-7 h and the dogs were nonviable when rewarmed.
Estimation of cyclic AMP turnover in normal and methylprednisolone-treated dogs: effect of catecholamines
Authors: Issekutz TB
Published: December 2017

The turnover rate of plasma cAMP was measured in unanesthetized normal and methylprednisolone (MP)-treated dogs with [8-3H]cAMP. Determination of specific activity was based on saturation of the specific binding protein, thus bypassing the need to know the plasma level of cAMP. In normal dogs the infusion of epinephrine increased plasma glucose by 33% and both the plasma level and rate of appearance (Ra) of cAMP 2.5-fold. Treatment with MP decreased the concentration as well as the turnover rate of cAMP by about 50%. It greatly potentiated not only the hyperglycemic effect (4-fold) of epinephrine but also the rise of plasma cAMP (8.5-fold) and that of Ra (6.8-fold). Norepinephrine infusion increased cAMP only by 50%. This effect was not potentiated by MP treatment and not altered by Na nicotinate. There was a linear correlation between plasma cAMP concentration and the rate of disappearance (Rd) of cAMP. It is concluded that: a) the increase of hepatic glycogenolysis is accompanied by a rise of cAMP output, whereas that of lipolysis is not; b) glucocorticoid treatment affects cAMP turnover; and c) the plasma level of cAMP is controlled by Ra, whereas Rd is the result of the mass-action effect of the concentration.
Hepatic bile acid transport: effect of conjugation and position of hydroxyl groups
Authors: Hoffman NE , Iser JH , Smallwood RA
Published: December 2017

The hepatic transport of five bile acids was studied in the bile-fistula rat. Pairs of labeled bile acids were injected simultaneously into the portal vein as a sharp pulse and the secretion of radiolabel in bile was measured over the nex 15 min. Six bile acid pairs were tested, and it was found that both conjugation and the number and disposition of hydroxyl groups influenced hepatic transport. Taurocholic acid was transported most efficiently, followed in order by glycocholic acid, cholic acid, deoxycholic acid, and chenodeoxycholic acid. Sampling aortic blood immediately after portal vein injection of labeled bile acid pairs demonstrated differential rates of hepatic extraction. In every comparison, the bile acid that was more efficiently extracted by the liver had a faster overall transport rate. This suggests that the differing rates of biliary secretion are, at least in part, determined by the efficiency of hepatic uptake.
Lack of a direct effect of efferent cardiac vagal nerve activity on atrial receptor activity
Authors: Wahab NS , Zucker IH , Gilmore JP
Published: December 2017

Experiments were carried out to determine the extent to which the efferent cardiac vagus may modulate the discharge from atrial receptors when heart rate was not controlled. Stimulation of the vagus increased atrial pressure and the discharge from type-B atrial receptors. In order to determine the extent to which the increase in atrial receptor discharge was the result of the associated hemodynamic changes, studies were done in which the vagus was stimulated while heart rate was maintained constant using atrioventricular pacing, as atrial pressure was varied over a wide range by volume expansion. In paced hearts vagal stimulation depressed atrial contractile force but did not alter atrial receptor discharge when compared to paced hearts without vagal stimulation. These results indicate that the effect of vagal stimulation on atrial receptor discharge is an indirect one mediated through the rise in atrial pressure due to cardiac slowing rather than a direct effect on the atrial stretch receptor itself.
Induced metabolic sequelae of tularemia in the rat: correlation with tissue damage
Authors: Powanda MC , Cockerell GL , Moe JB , Abeles FB , Pekarek RS , Canonico PG
Published: December 2017

Serum and liver zinc concentration, amino acid uptake by liver, seromucoid content, and alpha2-macrofetoprotein production were measured in vaccinated as well as nonimmune rats exposed to either virulent (SCHU S4) or attenuated (LVS) strains of Francisella tularensi. It appears that liver damage (pyogranulomatous lesions) must occur before there is any alteration in the above variables. The presence of bacteria in the liver is not of itself sufficient to lead to the onset of systemic, induced metabolic sequelae (IMS). The occurrence of zinc redistribution in all instances of increased serum protein synthesis may imply a necessary relationship between these two sequelae. Amino acid redistribution does not appear to be linked to serum protein synthesis. An endogenous mediator of systemic IMS can be detected in tularemic rats by injection of the serum of these animals into healthy recipients. The occurrence of zinc redistribution and increased serum protein synthesis in some groups of rats in the absence of amino acids uptake by liver, as well as the apparent differential dose responsiveness of these responses, are suggestive of a multiplicity of endogenous mediators.
Effect of secretin on electrical activity of small intestine
Authors: Mukhopadhyay AK , Johnson LR , Copeland EM , Weisbrodt NW
Published: December 2017

The effect of intravenously administered secretin (0.5, 2.0, 6.0 U/kg-h) and intraduodenal acidification (13.2 meq/h HCl) on the electrical activity of the small bowel of three conscious dogs with gastric and duodenal cannulas was observed. Electrical activity was recorded in fasted as well as fed conditions through silver wire electrodes implanted along the entire length of the small bowel. Intravenous infusion of secretin in all dosages and in all dogs delayed the onset of the interdigestive myoelectric complex and reduced the total percentage of slow waves with superimposed spike potentials. Intraduodenal acidification also inhibited the interdigestive myoelectric complex, which developed incompletely with fewer action potentials on slow waves. Secretin did not produce any alteration in the fed pattern of activity, slow-wave frequency, or the caudal migration of the interdigestive myoelectric complex. The present study indicates that the nuerohumoral mechanisms responsible for initiation of the interdigestive myoelectric complex may be different from those responsible for its caudal migration.
Hyporesponsiveness to glucoprivation during postnatal period in the rat
Authors: Gil-Ad I , Udeschini G , Cocchi D , Muller EE
Published: December 2017

2-Deoxy-D-glucose (2-DG), a glucose analogue, blocks glycolysis and induces intracellular glucoprivation. In the adult rat intraperitoneal administration of 2-DG or its injection into the lateral ventricle (IVT) of the brain induces hyperglycemia which is divorced from a rise in plasma insulin (IRI). In the present study, responsiveness to 2-DG-induced glucoprivation, after central or intraperitoneal injection of the drug, was studied in rats of 7, 14, 21, and 28 days of age and compared to that of the adult rat (50 days old). In 7-, 14-, 21-, and 28-day-old rats, the overall blood glucose (BG) response to IVT-injected 2-DG was equivalent to 4, 3.3, 17, and 33%, respectively, of the BG response present in the adult rat. Following intraperitoneal injection of 2-DG , the BG response evoked in the same age groups corresponded to 27, 31, 41, and 93%, respectively, of the adult response. Base-line plasma IRI levels were significantly lower in pups than in adults and increased progressively with age, but no difference was present in IRI levels between 2-DG-treated and control pups whether the 2-DG was given via the laterl ventricle or intraperitoneally. These results demonstrate the presence in the infant rat of clear-cut hyporesponsiveness to 2-DG-induced glucoprivation. The different response pattern between experiments involving central and peripheral 2-DG administration supports the existence of separate peripheral glucoreceptors for 2-DG and their earlier ontogenic activation. Since the infant mammal glucose is of minor relevance as an energy substrate, an interrelationship appears to be present between requirements for fuel(s) and homeostatic response to fuel deprivation.
Intestinal CaBP: a new quantitive index of vitamin D deficiency in the rat
Authors: Bronner F , Freund T
Published: December 2017

Rats raised from weaning on regiments adequate in calcium and phosphorus but deficient in vitamin D will have no detectable intestinal calcium-binding proteins (CaBP), whether or not they show other signs of vitamin D deficiency, such as hypocalcemia. When hypocalcemic, vitamin D-deficient animals were treated with 25-hydroxycholecalciferol, a vitamin D metabolite, they showed a dose-dependent increase in plasma calcium and CaBP; both responses can be described by a single linear relationship, which appears to apply whether the metabolite is 25-hydroxycholecalciferol or dihydrotachysterol. Since vitamin D status is only one determinant of plasma calcium, whereas CaBP (or its expression) appears to depend on vitamin D quantitatively, CaBP may be used as an index of vitamin D status, provided calcium intake is controlled.
Vascular volume-distensibility characteristics of the isolated dogfish gut
Authors: Opdyke DF , Wilde DW
Published: December 2017

The vascular capacitance and volume distensibility of the isolated dogfish gut and segments of dogfish arteries and veins were investigated. The volume-distensibility curves for dogfish arteries and veins are very similar to comparable curves derived from arteries and veins of dogs or man. The vascular volume-distensibility curve of the gut, however, shows a greater distensibility at higher systemic pressure than at lower pressure. Evidence is presented that significant amounts of fluid leave the vascular compartment at a lower systemic pressure than in an isolated dog hindlimb preparation. However, this alone does not explain the atypical vascular volume-distensibility curve obtained from the dogfish gut. It is suggested that in the dogfish capillary filtration pore enlargement takes place at a very low capillary pressure or volume (compared to mammals) and this complicates the construction of a volume-distensibility curve because initial vascular volume is not constant.
Cellular basis for reversal of hyperkalemic electrocardiographic changes by sodium
Authors: Ballantyne F , Davis LD , Reynolds EW
Published: December 2017

We examined the hypothesis that reversal of hyponatremic hyperkalemic electrocardiographic changes through the infusion of saline solutions was due to the action of sodium ion in increasing the action potential rising velocity which is depressed when the cell is exposed to increasing concentrations of potassium. Using standard microelectrode techniques, the rising velocity of canine ventricular cells was shown to increase by 21%, whereas conduction time between two microelectrodes decreased 17% when the sodium concentration of the perfusate was increased from 120 to 163 mM in 2.7 mM potassium solution. When these cells were exposed to identical increases in sodium concentration in a 7.7-mM potassium solution, rising velocity increased 55% (P less than 0.005), whereas interelectrode conduction time decreased 33% (P less than 0.05). Similar changes were noted in experiments on human ventricular cells. These experimental findings are consistent with the hypothesis stated above.
Ionic requirements of proximal tubular sodium transport. II. Hydrogen ion
Authors: Green R , Giebisch G
Published: December 2017

Simultaneous perfusion to proximal convoluted tubules and peritubular capillaries was used to study the effects of different perfusion fluids on sodium reabsorption and hydrogen secretion, which was calculated as bicarbonate reabsorption and titratable acid. Results show that sodium reabsorption was not tightly coupled to hydrogen secretion. Bicarbonate stimulates both sodium reabsorption and hydrogen secretion, but Tris stimulates only sodium reabsorption. Imposing an adverse chloride gradient across the proximal tubule (C1- peritubular greater than C1- luminal) decreased sodium reabsorption but did not diminish hydrogen secretion. Diamox inhibited both net sodium and hydrogen transport. It is concluded that there is not firm linkage between sodium reabsorption and hydrogen secretion and that bicarbonate probably stimulates sodium transport by a number of mechanisms, including an effect on the sodium transport unrelated to its ability to increase hydrogen ion secretion.
Role of calcium in bone maturation arrest after thyroparathyroidectomy in the rat
Authors: Burnell J. M. , Teubner E. , Korn D. , Miller A.
Published: December 2017

Thyroparathyroidectomy in the rat results in decreased plasma calcium and magnesium and increased phosphorus. The associated bone changes are decreased calcium, hydroxyproline, carbonate, and wholebone density. Bone magnesium, sodium, mineral density, and percent crystallinity are increased. The delayed matrix formation and mineralization previously identified by histologic techniques are herein characterized by direct measurement as arrest of the normal increase of hydroxyproline/matrix and percent mineral. The bone mineral present is of high density and x-ray-diffraction crystallinity, suggesting a decrease in the mineralization front high in the amorphous phase and/or small nondiffracting crystalloids. The chemical studies reveal that in the absence of available Ca, Mg and Na are substituted, and CO3 is decreased. The restoration of these plasma and bone abnormalities to normal by a diet high in CaCO3 adds further emphasis to the essential role of Ca in bone cell function.
Dynamics of glomerular ultrafiltration. IX. Effects of plasma protein concentration
Authors: Baylis C. , Ichikawa I. , Willis W. T. , Wilson C. B. , Brenner B. M.
Published: December 2017

Experiments were carried out on 42 Munich-Wistar rats with surface glomeruli accessible to micropuncture to investigate the effects of reduction in systemic plasma protein concentration. CA, and thus afferent oncotic pressure, IIA, on the determinants of glomerular ultrafiltration. In animals in which CA was reduced by a variety of maneuvers, observed values for single-nephron GFR were lower than values predicted by the Starling relation, when the latter were calculated assuming that the observed increase in the net driving pressure for ultrafiltration (due to the reduction in IIA) was the only factor perturbed. In all experimental conditions where CA was reduced, rats were invariably observed to be at filtration pressure disequilibrium, permitting calculation of unique values of the ultrafiltration coefficient, Kt. In all low-CA groups, mean values of Kf were uniformly lower than values obtainedin normoproteinemic control animals. The failure of SNGFR to rise to predicted values when CA is reduced is therefore due to the concomitant reduction in Kf. No morphological basis for this reduction in Kf was discerned.
Antidiuretic hormone and the distribution of renal cortical blood flow
Authors: Johnson M. D. , Park C. S. , Malvin R. L.
Published: December 2017

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.
Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs
Authors: Hulter H. N. , Ilnicki L. P. , Harbottle J. A. , Sebastian A.
Published: December 2017

When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.
Mechanism of intrarenal blood flow redistribution after carotid artery occlusion
Authors: Prosnitz E. H. , Zambraski E. J. , DiBona G. F.
Published: December 2017

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.
Effects of high potassium concentration on theophylline responses of toad bladder
Authors: Mendoza S. A. , Nakamoto K. K.
Published: December 2017

It has been demonstrated previously that a high concentration of potassium in the serosal bathing medium (5–21.5 mM) potentiates the increase in short-circuit current caused by vasopressin or exogenous cyclic AMP. The same concentration of potassium in the bathing medium inhibited the increase in short-circuit current caused by theophylline. The increases in osmotic water permeability caused by vasopressin or cyclic AMP were unaffected by a serosal potassium concentration of 21.5 mM. The increase in osmotic water permeability caused by theophylline was inhibited by 21.5 mM potassium. The concentration of cyclic AMP in either intact total bladder or isolated toad bladder cells was increased two- or three-fold by theophylline. Increasing the concentration of potassium to 21.5 mM did not alter cyclic AMP concentration in either the absence of presence of theophylline. One interpretation of these results is that theophylline increases osmotic water flow and short-circuit current by a mechanism other than by inhibition of cyclic nucleotide phosphodiesterase.
Monovalent cation and ouabain effects on PAH uptake by rabbit kidney slices
Authors: Podevin R. A. , Boumendil-Podevin E. F.
Published: December 2017

The effects of K+, Na+, and ouabain on para-aminohippurate (PAH) accumulation by rabbit kidney slices have been further examined. The present studies show that for maximum uptake of PAH to occur in Na+,K+-depleted slices extra-cellular Na+ and K+ ions are required together. Kinetic studies revealed that increasing the external K+ from 0 to 5 mM caused a decrease in the apparent Km of transport. The Vmax values were not changed significantly. In the presence of 5 mM K+, increasing Na+ concentration in the bathing medium from 0 to 145 mM produced an increase in the V max while the apparent Km remained constant. In the presence of 5 mM external K+, ouabain inhibition of PAH uptake was progressively and entirely antagonized by decreasing external Na+. Studies on kidney slices treated with ouabain in a Na+,K+-free medium in order to inhibit active electrolyte transport showed that PAH uptake under anaerobic conditions was specifically enhanced by Na+. This stimulation occurred when cell [Na+] was less than medium [Na+]. This Na+-dependent and energy-independent accumulation of PAH was inhibited by hippuric acid but not by N-methylnicotinamide.
Use of inhibitors in physiological studies of carbonic anhydrase
Authors: Maren T. H.
Published: December 2017

The appropriate use of acetazolamide in examining physiological function is based on the following: 1) the dissociation constant of the drug-carbonic anhydrase complex (10(-8) M); 2) the concentration needed to eliminate the catalyzed reaction (10(-4) M can be achieved readily in tissues by giving 20 mg/kg at no toxicity; and 4) the lack of known effects on any other systems at concentrations below 10(-3) M. Several problems have been identified and are analyzed concerning the use of acetazolamide and allied drugs. Concentrations greater than 10(-3) M have been used in vitro and occasionally in vivo, generating nonspecific effects. Experiments in which the substrate (CO2) is varied over a large range have been interpreted without regard to alteration in both the catalyzed and uncatalyzed rates, leading to conclusions that acetazolamide acts on a transport system other than carbonic anhydrase, while in reality the drug is acting on carbonic anhydrase at different levels of its catalytic rate. Since calculation of the uncatalyzed hydration of CO2 or dehydration of HCO3-in tissues involves some uncertainty, these rates are generally best defined by studying the dose-response curves of inhibitors and observing the residual activity after full inhibition. The kidney is an exception, since here the residual rate also involves an entirely separate process. Inhibitors other than acetazolamide are useful in ruling out nonspecific effects, and in gaining certainty of access to cells. Compounds closely akin to the inhibitors, but lacking action upon carbonic anhydrase, are also available as controls. It is emphasized that acetazolamide and other carbonic anhydrase inhibitors, when properly used, are highly specific probes of a single enzyme that has a wide variety of physiological functions.
Effects of insulin, ADH, and cyclic AMP on sodium transport in the toad bladder
Authors: Wiesmann W. P. , Sinha S. , Klahr S.
Published: December 2017

These studies further define the mechanisms by which insulin stimulates Na transport in the toad bladder. Serosal but not mucosal addition of insulin, 100-1,000 mU/ml, stimulated short-circuit current (SCC) by 25-50%. The initial rise in SCC occurred at 5 min and the peak response at 15-25 min. Doses of insulin greater than 250 mU/ml increased SCC values for up to 3 h. Actinomycin D did not block the early rise in SCC produced by insulin, but it blocked the delayed effects. Insulin increased SCC in substrate-depleted bladders, although the increase in SCC was less (P less than 0.01) than in nonsubstrate-depleted bladders. Pyruvate addition to substrate-depleted bladders restored to normal the rise in SCC observed after insulin. Simultaneous addition of ADH and insulin led to an increase in SCC that was greater than the sum of the responses observed when each hormone was added independently. Synergistic effects on SCC were also obtained with cyclic AMP and insulin. Insulin did not increase cyclic AMP levels in toad bladder epithelial cells. It is suggested that insulin stimulates active Na transport by two mechanisms: 1) a rapid phase, which may involve unmasking of pump sites within the membrane, and 2) a delayed effect which seems to require protein synthesis. The synergism of which seems to require protein synthesis. The synergism of insulin with ADH or cyclic AMP may reflect a facilitative effect of insulin on ADH or cyclic AMP-sensitive pump sites or, alternatively, the uncovering of latent pump sites that then may be available to stimulation by ADH or cyclic AMP.
Handling of angiotensin II and oxytocin by renal tubular segments perfused in vitro
Authors: Peterson D. R. , Oparil S. , Flouret G. , Carone F. A.
Published: December 2017

In order to study renal tubular handling of two small peptide hormones, [14c]angiotensin II ([14C]AII) and [3H]oxytocin ([3H]OT) were microperfused through rabbit kidney tubule segments in vitro. The reabsorption and tubular sequestration of radioactive label were determined, and the collection fluid was electrophoretically analyzed. The data suggest that [14C]AII is extensively hydrolyzed in the pars recta of the nephron and is rapidly reabsorbed across the tubular epithelium. Under similar experimental conditions, hydrolysis of [3H]OT was not observed in either the proximal straight or cortical collecting tubule segment, and the rate of reabsorption was low. Thus, tubular handling of OT appears to differ from that of AII, probably because of differences in molecular structure.
Renal vasopressin clearance with reductions in renal blood flow in the dog
Authors: Shade R. E. , Share L.
Published: December 2017

These! experiments were designed to evaluate directly the effects of a reduction in renal blood flow on the renal metabolism of vasopressin (ADH) in the anesthetized dog...
Origin of electrical PD's in hamster thin ascending limbs of Henle's loop
Authors: Marsh D. J. , Martin C. M.
Published: December 2017

Microelectrodes with 2-micronm-tip diameters arranged to record differentially between this ascending limbs (ALH) and ascending vasa recta (AVR), gave values of 1.95 +/- 0.17 mV, ALH positive, in hydropenia with mineral oil bathing the kidney. Average values remained in the range of 1-2 mV when the ALH and AVR values were obtained sequentially, when the kidney was bathed in Ringer solution, when 5-8 Momega Ling-Gerard microelectrodes were used in the ALH, or when the hamsters were in saline diuresis. These results contradict reports of earlier studies with high impedance Ling-Gerard electrodes that the PD was -9 mV, ALH negative. Perfusion of ALH in saline diuresis with solutions of various compositions provided estimates of ionic transport numbers: tNa+ = 0.33 +/- 0.01, tK+ = 0.00 +/- 0.02, tC1- = 0.67 +/- 0.02. When the perfusion solution was designed to have the same Na+, K+, and C1- concentrations as AVR plasma, the PD was 1.36 +/- .20 mV; when ouabain or furosemide were included (10(-5) M), the PD declined 1.35 +/- 0.21 mV and 1.41 +/- 0.28 mV, respectively. The results suggest that active C1- transport is mainly responsible for the PD, but that diffusion potentials can contribute.
Cyclic AMP in action of antidiuretic hormone: effects of exogenous cyclic AMP and its new analogue
Authors: Hall D. A. , Barnes L. D. , Dousa T. P.
Published: December 2017

Exogenous cyclic 3',5'-adenosine monophosphate (cAMP) stimulates the effect of the antidiuretic hormone, vasopressin (VP), only in pharmacologic quantities and results have often been inconsistent. The present study examined the ability of a new analogue, 8-[p-Cl-phenylthio]cyclic 3',5'-adenosine monophosphate (C1-PheS-cAMP) to mimic the effect of VP, both biochemically (protein kinase activation) and functionally (hydrosomatic response of perfused collecting tubules) in mammalian kidney tissue. C1PheS-cAMP was found to be about 100 times as effective as cAMP both biochemically and functionally. The increased effectiveness of C1PheS-cAMP is probably is probably due to a greater permeability across the cell membrane and to the resistance of C1PheS-cAMP to enzymatic degradation, Cyclic AMP phosphodiesterase inhibition was observed with C1PheS-cAMP, but its contribution to overall effect was minor. C1PheS-cAMP was found to be more effective than exogenous vasopressin, an effect probably due primarily to its resistance to catabolism. The results provide further new evidence that cAMP and protein kinase are involved in the cellular action of vasopressin. C1PheS-cAMP proved to be a useful tool in the study of hormone action, especially in steps subsequent to cAMP generation.
Movement of p-aminohippurate between lumen and cells of renal tubule
Authors: Foulkes E. C.
Published: December 2017

This study explores the role of brush border (luminal) membranes in p-aminohippurate (PAH) transport by the rabbit kidney. Under control conditions PAH appears in urine at the same rate as simultaneously injected inulin; no evidence for a secretory delay was found. After suppression of secretion by limiting concentrations of Benemid (probenecid), urinary PAH is largely derived from glomerular filtrate: its tubular transit time exceeds that of inulin. Excess Benemid abolishes this delay. Filtered PAH on its way to excretion appears to be permitted by a mechanism sensitive to high concentrations of Benemid to pass through an extraluminal volume equivalent to that of the proximal tubule cells. These results strengthen the previously suggested model for tubular PAH transport, and provide justification for use of glomerulus-to-ureter transit times in localizing tubular transport mechanisms.
Effect of furosemide on renal handling of glucose in the rat
Authors: Boonjarern S. , Mehta P. K. , Laski M. E. , Earnest W. R. , Kurtzman N. A.
Published: December 2017

Clearance and intratubular microinjection studies were performed in rats during extracellular volume expansion before and after furosemide administration to evaluate renal tubular transport of glucose. Three groups of animals were studied: group I, intact rats; group II, acutely thyroparathyroidectomized rats; and group III, thyroparathyroidectomized rats receiving parathyroid extract after a control period. In all groups furosemide caused a significant increase in the urinary flow rate and sodium excretion. There was no significant change in filtered glucose and glucose excretion. After early distal tubular injections of [14C]glucose, recovery was complete both before and after furosemide infusion. Furosemide had no effect on [14C]glucose recovery after the late proximal injection. These results indicate that furosemide has no effect on the renal handling of glucose in normoglycemic rats. There is no evidence for glucose reabsorption in the nephronal segments distal to the early distal tubular segment in this experimental state. Our data suggest, but do not prove, that no glucose is transported by the rat nephron beyond the pars recta during normoglycemia.
Relations of renal transport rate, transport maximum, and competitor potency for tetraethylammonium and choline
Authors: Rennick B. , Acara M. , Glor M.
Published: December 2017

By use of the Sperber technique in chickens, the renal tubule transport maximum (Tm) for the organic cation tetraethylammonium (TEA) was determined in vivo. The tubular transport rate, the Tm, and the competitor potency are assumed to have causal relationships. It was demonstrated that the two cations TEA and choline compete for the tubular transport of [14C]TEA. The saturating load of one cation was reduced by the simultaneous presence of the other. The Tm for these two cations was different by a factor of 2.4 and their respective competitor potency was inversely related to their Tm.
Characteristics of accumulation of probenecid by rabbit kidney cortical slices
Authors: Sheikh M. I. , Stahl M.
Published: December 2017

Probenecid was accumulated by renal tissue both under aerobic and anaerobic conditions. The aerobic uptake at a low medium concentration of probenecid was enhanced three- or fourfold by acetate, while metabolic inhibitors and organic anions like p-aminohippurate (PAH), phenol red, and other substituted phenolsulphonphthalein (PSP) dyes which undergo secretion had an inhibitory effect. Octanoate and succinate stimulated aerobic probenecid uptake at low medium concentrations, but inhibited transport of the drug at high levels. Studies on renal homogenates showed that the anaerobic uptake of probenecid is due to binding to tissue constituents. Binding characteristics of PSP dyes to phospholipid vesicles and a representative binding protein, human serum albumin, exhibited close similarity to that of binding to renal tissue. Hydrophobic compounds like octanoate and PSP dyes partially inhibited probenecid binding. In contrast, transport of probenecid was almost completely abolished by these substances and PAH at high medium concentrations. On the basis of the results presented in this paper, it is concluded that renal transport of probenecid occurs by the common organic anion transport system.
Ouabain, acetazolamide, and Cl-flux in isolated frog skin: evidence for two distinct active Cl-transport mechanisms
Authors: Watlington C. O. , Jessee S. D. , Baldwin G.
Published: December 2017

Two distinctly different mechanisms for active Cl- transport in epithelia may exist: one, ouabain-sensitive and cation-dependent, and the other, acetazolamide-sensitive and cation-independent. As a test of this hypothesis the three active Cl- transport systems in isolated short-circuited skin of Rana pipiens were examined. Sensitivity to ouabain (10(-4) M) and acetazolamide (5 X 10(-3) M) and dependence on Na+ and K+ in the medium were ascertained. The first system, net chloride influx in ordinary Ringer, exhibited specific ouabain sensitivity and acetazolamide insensitivity. As we have previously shown this system to be clearly dependent on Na+ on the cis and K+ on the trans side, cation dependence was not re-studied. The second system, isoproterenol-stimulated net Cl- outflux, was also ouabain-sensitive and acetazolamide-insensitive. It was dependent on the presence of Na+ on the cis side, but the K+ dependence was less clear. In contrast to the first two, the third system (net influx in low Cl- medium sulfate Ringer containing 2.4 mM Cl-) was largely ouabain-insensitive, completely acetazolamide-sensitive and independent of both Na+ and K+. Thus, the hypothesis of two distinct mechanisms seems to hold for the three active Cl- transport systems in frog skin. Data from various other Cl- transporting epithelia are examined, and the general applicability of such a scheme of categorization for active Cl- transport mechanisms is discussed.
Vasopressor role of ADH in the pathogenesis of malignant DOC hypertension
Authors: Möhring J. , Möhring B. , Petri M. , Haack D.
Published: December 2017

Page F260: J. Möhring, B. Möhring, M. Petri, and D. Haack. “Vasopressor role of ADH in the pathogenesis of malignant DOC hypertension.” Page F264: left column, lines 1, 2, and 3—substitute ng (nanograms) for μg (micrograms).
Parasympathetic control of Na, K transport in perfused submaxillary duct of the rat
Authors: Schneyer L. H.
Published: December 2017

The effects of stimulating the parasympathetic innervation to rat submaxillary gland on ductal transport of Na, K, water, and transepithelial PD, were tested in the main excretory duct during perfusion through its lumen. During nerve stimulation, transepithelial PD was consistently decreased, usually by about 15 mV, and this decrease could be blocked by atropine but not by adrenergic blocking agents. Net flux of Na, K, or water was not significantly changed during stimulation. One-way flux of Na from the lumen also was unaffected. The decrease in PD during stimulation was not affected by substituting isethionate for Cl or increasing [K] in the luminal perfusion medium. It is concluded that parasympathetic effects are exerted on the ductal cells, but that these probably do not involve conductance changes at the luminal membrane.
Renal extraction of glucagon in rats with normal and reduced renal function
Authors: Bastl C. , Finkelstein F. O. , Sherwin R. , Hendler R. , Felig P. , Hayslett J. P.
Published: December 2017

To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.
Phosphate transport in superficial and deep nephrons in phosphate-loaded rats
Authors: Knox F. G. , Haas J. A. , Berndt T. , Marchand G. R. , Youngberg S. P.
Published: December 2017

We tested the hypothesis that greater phosphate delivery from deep nephrons than from superficial nephrons contributes to the addition of phosphate to the collecting system during phosphate loading. In the first group of eight anesthetized Munich-Wistar rats infused with phosphate and parathyroid hormone (PTH), fractional delivery of phosphate (FDP%) from superficial distal tubules was 56 +/- 6%, significantly less than the amount appearing in the urine, 67 +/- 6% (P less than 0.01). In the second group of six rats, we determined whether this addition of phosphate could be accounted for by a higher FDP% from the deep nephrons. Free-flow micropuncture collections were taken from deep nephrons (ascending limb of the loop of Henle in the papilla), superficial nephrons (distal tubules in the cortex), and urine (duct of Bellini). The FDP% to the ascending limb of the loop of Henle in deep nephrons was 78 +/- 10%, significantly greater than to the distal convoluted tubules in superficial nephrons, 51 +/- 6% (P less than 0.005), and the fractional excretion of phosphate in urine, 72 +/- 10% (P less than 0.05). Although a difference between FDP% in superficial and deep nephrons due to reabsorption in the ascending limb of the loop of Henle cannot be ruled out from the present data, other studies indicate that this interpretation is unlikely. We conclude that greater phosphate delivery by deep nephrons contributes to the addition of phosphate to the collecting system of phosphate-loaded rats.
Feedback control of glomerular filtration rate in isolated, blood-perfused dog kidneys
Authors: Schnermann J. , Stowe N. , Yarimizu S. , Magnsusson M. , Tingwald G.
Published: December 2017

Micropuncture studies were done in isolated, blood-perfused dog kidneys to investigate the intrarenal nature of tubuloglomerular feedback regulation of nephron filtration rate. Collections were made at early proximal tubular sites during alterations in flow through the loop of Henle to elicit the feedback response. Renal blood flow in the 10 isolated kidneys averaged 4 ml/ min-g kidney after an initial vasoconstriction. Filtration rate was 0.52 +/- 0.12 ml/min-g kidney for the period 90–120 min, but progressively fell after 120 min, as did fractional sodium reabsorption and PAH extraction. The feedback regulation of nephron filtration rate was demonstrated during the first 3 hrs of perfusion even with subnormal renal function. The feedback response expressed as the percent reduction of early proximal flow rate when loop of Henle flow was elevated from 0 to 45 nl/min was 41.3 +/- 4.5 (for the first 90 min), 35.3 +/- 7.5 (90-120 min), 24.3 +/- 6.8 (120-150 min), and 26.6 +/- 7.7% (150-180 min). After 180 min, the feedback response was no longer demonstrated. These results show that feedback-induced changes in nephron filtration rate are achieved in the absence of nervous system influences.
Development of chronic perinephritic hypertension in dogs without volume expansion
Authors: Freeman R. H. , Davis J. O. , Watkins B. E.
Published: December 2017

The theory of whole body autoregulation to explain the pathogenesis of experimental renal hypertension states that hypertension is initiated in response to an early increase in salt and water retention and a subsequent elevation of the cardiac output. This hypothesis was evaluated in the present study. Dogs (n,5) were made hypertensive by wrapping the left kidney in cellophane and removing the contralateral kidney 3 wk later. One week prior to right nephrectomy, the dogs were volume depleted by placing them on a low sodium intake (less than 3 meq of sodium/day) and giving them a mercurial diuretic for the first 3 days of the diet. This superimposed sodium depletion (negative sodium balance of 137 +/- 17 meq) increased plasma renin activity 3-5 times but did not change arterial pressure or heart rate. Within 2 days after nephrectomy, the mean arterial pressure increased from the control level of 105 +/- 1 to 135 +/- 6 mmHg (P less than 0.005) and pressure remained elevated throughout an additional 4-wk period in which volume depletion was enforced. The present study suggests, therefore, that initial blood volume expansion with such possible consequences as elevated cardiac output are not essential to the pathogenesis of experimental renal hypertension.