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Previous studies have established that during orthograde perfusion from a late proximal tubule site, there is a direct relationship between the magnitude of the feedback response and the level of distal tubular fluid sodium chloride concentration. The present study was conducted in the rat to extend this observation by assessing stop flow pressure (SFP) feedback responses during retrograde perfusion into the early distal tubule with solutions varying in total solute concentration and in the anionic constituent. SFP was measured after blockade of the intermediate proximal and late distal tubular segments with wax. Retrograde perfusion was initiated from an early distal tubular site at 15 nl/min. All solutions contained a 38 mOsm/kg matrix base, and the total solute concentration was increased with either sodium chloride or sodium isethionate to achieve osmolalities of 68, 85, and 120 mOsm/kg. For comparison, feedback responses during perfusion with a 120 mOsm/kg choline chloride solution were evaluated. During perfusion with the 120 mOsm/kg solutions, SFP decreased by 13 +/- 1.3 mm Hg with the sodium chloride solution, 12 +/- 1.5 mm Hg with the sodium isethionate solution, and 12 +/- 1.3 mm Hg with the choline chloride solution. During perfusion with solutions having an osmolality of 85 mOsm/kg, SFP decreased by 8 +/- 1.3 mm Hg with sodium chloride and 8 +/- 0.8 mm Hg with sodium isethionate. The 68 mOsm/kg solutions elicited decreases in SFP of 4.4 +/- 0.4 mm Hg and 5 +/- 0.5 mm Hg. During perfusion with the 38 mOsm/kg matrix solution, SFP decreased by an average of 1.4 +/- 0.9 mm Hg. Linear regression analysis revealed a 1 mm Hg decrease in SFP for every 7.7 mOsm/kg decrease in perfusate osmolality below 120 mOsm/kg. These results confirm previous findings that the magnitude of the feedback response is associated closely with the concentration of the perfusate over a narrow range from 38 to 120 mOsm/kg. Since the responses with sodium isethionate solutions were similar to the responses obtained with sodium chloride containing solutions, these studies provide evidence that the magnitude of the feedback responses are not specifically dependent on alterations in chloride concentration.

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

The structural organization of the transcribed loops of lampbrush chromosomes present in the vegetative nuclei of the green algae, Acetabularia mediterranea and A. crenulata, and in oocyte nuclei of the newt, Pleurodeles waltlii, has been studied by electron microscopy of relatively thick (100--200 nm) and ultrathin sections through chromosomes prepared and fixed at physiological salt concentrations. The procedure allows the direct comparison of the same chromosome or chromosome region by light and electron microscopy, that means identification of the transcriptional arrays in specific loops. After such preparations the loop axis reveals regions that are smoothly-contoured ("non-beaded") and only 4 to 7 nm thick and are clearly different from supranucleosomal forms of inactive chromatin fibrils as well as from extended filaments of nucleosomal granules examined in parallel. This indicates that the chromatin of the loops axis of intensely transcribed regions is in a structural form different from that of non-transcribed chromatin. A similarly thin axis has been identified in loops of chromosomes of nuclei fixed in situ. The lateral ribonucleoprotein (RNP) fibrils associated with transcribed loop regions appear as serial arrays of granules, often of regular size, which are smaller in the chromosomes of Acetabularia (mean diameter 18 nm) than in those of amphibia (mean diameter 28 nm). Discontinuous arrays of lateral RNP fibrils and fibril arrays with different polarity are found in some loops. Certain loops and loop regions are characterized by specific patterns of aggregation of such lateral RNP fibrils which appear to correspond to the "granules" visible in these loops in the light microscope. The observations show that arrays of transcriptional complexes in chromosome loops can be visualized in thin sections of material prepared at physiological ionic strength with similar resolution and clarity as in spread preparations of chromosomal material dispersed in extremely low salts buffers. The results are interpreted to approximate the organization of loop structures in vivo and to show that, at physiological ionic strength, the chromatin of the loop axis is organized in a form different from that characteristic of non-transcribed chromatin.

In order to establish the in vivo specificity of the mineralocorticoid recognition system of the rat brain, we investigated the potencies of aldosterone (ALDO) and corticosterone (CORT) in suppressing salt intake in adrenalectomized (ADX) rats. Increasing doses of ALDO (25, 50 and 100 ng/h), administered by Alzet minipump, suppress salt intake in a two-bottle preference test. CORT in doses up to 50 micrograms/h failed to mimic this effect of ALDO or to block it. Using the 50 micrograms/h dose of CORT, we demonstrated that the forebrain uptake of 3H-ALDO in vivo is suppressed by 60-75% when measured by isolation of cell nuclei or by quantitative autoradiography. The suppression is especially marked in the hippocampal formation, amygdala and septum, sites which also accumulate high levels of 3H-CORT. The uptake of 3H-ALDO by ADX rat forebrain can be suppressed approximately 95% by infusion of a specific antimineralocorticoid, RU 28318, at a dose of 50 micrograms/h. This dose also blocks ALDO action on salt intake. Lower doses of RU 28318 fail to block ALDO action or brain 3H-ALDO uptake. We conclude that: (1) ALDO is at least 500-fold more potent in vivo than CORT as a mineralocorticoid. (2) High uptake of 3H-ALDO in vivo by hippocampal formation, amygdala and septum in ADX rats is due in large part to binding to sites preferentially suppressed by CORT. The 3H-ALDO uptake (ca. 30%) after suppression by stress levels of CORT shows a regional distribution in which uptake is slightly higher in circumventricular structures than in hippocampal formation, septum or amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramuscular injections of long-acting synthetic ACTH (45 U twice daily for 5 days) caused a large increase in the intake of 0.5 M NaCl in sheep. Mean Na intake of the sheep on the last 3 days of treatment approximated 50% of their total extracellular fluid Na. The mineral appetite was specific for NaCl. Intakes of 0.5 M KCl or 0.25 M CaCl2 were not significantly altered. The enhanced appetite for Na induced by ACTH appeared to precede any increase in urinary Na excretion. ACTH treatment was ineffective in adrenalectomized sheep. However, an infusion into adrenalectomized sheep of a combination of adrenal steroid hormones (including aldosterone, deoxycorticosterone, 11-deoxycortisol, cortisol, and corticosterone) that contrived blood levels similar to those, obtained with ACTH treatment in normal sheep did induce Na appetite. Thus, ACTH induces a specific, adrenal-steroid hormone-dependent Na appetite in sheep.

Adult Rana temporaria, acclimated to tap water or hyperosmotic (0.9% NaCl saline) media, were injected with Acetazolamide, Frusemide, or Captopril, or were nephrectomized and injected with captopril. Saline-injected animals served as controls. Total water flux and drinking rates were determined by body weight changes and by the rate of accumulation of an environmental marker (phenol red) in the gut, respectively. Changes in plasma corticosteroids and ion concentrations were also assessed. Acetazolamide and frusemide produced hyponatraemia in tap water-acclimated animals, but induced increased aldosterone levels in frogs in both environments. Captopril reduced body weight and aldosterone levels of tap water frogs, but had no effect on plasma ion composition. Animals treated with captopril on immersion in saline had plasma hypoosmotic to their environment. Saline-acclimated frogs drank less environmental water than did those in tap water. Captopril, acetazolamide, and frusemide all stimulated drinking rates of saline-acclimated frogs; captopril, however, had no effect on the drinking rates of nephrectomized animals, indicating that the dipsogenic actions of this drug are probably reflected by inhibition of the renin-angiotensin system. In tap water animals, acetazolamide stimulated drinking, while frusemide stimulated integumental water uptake. No correlation was apparent between plasma aldosterone and corticosterone concentrations, or between changes in body weight and drinking rates. This suggests that there are independent mechanisms controlling aldosterone and corticosterone secretion, as well as integumentary and buccal uptake of water in R. temporaria.

The interrelationship between diet, blood pressure and the acceptability of salt solutions was examined. Sprague-Dawley rats were fed high carbohydrate (5% corn oil), all unsaturated fat (20% corn oil) or all saturated fat (20% coconut oil) diets containing either basal (0.15% NaCl) or high (8.0% NaCl) levels of salt. Systolic blood pressure was determined indirectly using an electro-sphygmomanometer. Percent acceptance was determined using a two-bottle preference test. Results from this experiment suggest that postingestional feedback mechanisms rather than blood pressure play an important role in determining the acceptability of salt solutions by the Sprague-Dawley rat.

Two- and five-day old chicks were injected intraventricularly with D-proline and structurally related compounds. D-proline produced convulsions and lethality, but was non-amnestic, whereas the naturally-occurring isomer, L-proline, was non-convulsant and non-toxic but amnestic. D-proline convulsions were accompanied by decreased high frequency in the EEG and increased slow wave activity. High amplitude spiking was not observed. The lethality of D-proline was saline-dependent. Control experiments ruled out possible toxic factors such as hypertonicity, pH pyrogens, injection volume, or needle misplacement. The results demonstrate that saline and distilled water are not equivalent injection vehicles. A sodium-free vehicle may lead to artifacts but is advantageous in experiments in which amino acid transport must be minimized.

In photoelectric plethysmography a distinction is made between the reflection methods. Uncertainties still exist, especially regarding the origin of the reflected signal: some investigators attach quantitative value to the amplitude of the plethysmogram. The various findings are reconsidered. Various fluids are pulsatingly pumped through an in vitro circuit. Flow, pressure and volume pulsations are measured, as is the total light intensity detected by a photoelectric plethysmograph with the small variations caused in it by the pulsations in flow. Both phase and amplitude of the resulting plethysmogram are studied and the results compared with those found in vivo at the fingers and auricles. In vitro, the variations in light reflection are in phase with the volume pulsations: this can only be ascribed to reflection by orienting erythrocytes. In vivo, however, the light reflection, like the light transmission, is in anti-phase with the volume excursions, thus eliminating the determinative effect of light reflection by orienting erythrocytes--the strong reflection from surrounding tissues completely dominates reflection from erythrocytes. Since erythrocytes also have absorptive properties, and the light reflection is in anti-phase with the volume excursions, it is concluded that this absorptivity can manifest itself over the strong reflection from surrounding tissue. In vivo, therefore, the reflection plethysmogram is, in principle, an absorption measurement. The relationship between intensity of detected light and resultant voltage may not be linear: this nonlinearity may not be neglected when amplitude changes are compared. Amplitude changes of different plethysmograms may only be compared quantitatively if there is no difference in their light-voltage relationship.

Single-channel recording by the patch-clamp technique has now characterized three kinds of membrane potassium channels activated by intracellular calcium ions in animal cells. These play a crucial part in the regulation of membrane potential and of secretion.

A number of possible modes of coupling of sodium chloride transport have been considered, and their roles in the various parts of the renal tubule have been reviewed. Many modes of coupling have been found in various combinations in one or another of the segments. Of special interest are the observations of carrier coupling of sodium to chloride transport in some of the segments, such as the thick ascending limbs of Henle's loop.

Systolic blood pressure was determined weekly to assess the development of hypertension in sedentary and active Dahl salt-sensitive (S) rats that were exercised by running at 20 m/min, 60 min/day, 5 days/wk. The marked rise in blood pressure that occurred with feeding 8% NaCl (wt/wt) diet in Dahl S rats could be attenuated by chronically practiced endurance running, but only if exercise at 20 m/min was started at the beginning of salt feeding. Under the same dietary feeding conditions, running at 27 m/min resulted in incomplete attenuation of hypertension. Further, running for 30 min/day was not as beneficial as running 60 min/day at 20 m/min. Delaying the start of exercise for 6 wk after the beginning of salt feeding did not result in reduction of hypertension in the S rat. These experiments indicate that increases in blood pressure can be prevented in Dahl S rats for 12 wk if running is initiated concomitantly with salt feeding. Blood pressure is not reduced if hypertension due to salt feeding has been continued for 6 wk. The results also indicate that there is an optimal exercise intensity, duration, or both, for controlling hypertension in Dahl rats.

Mechanisms for urinary concentration or dilution depend on counterflow processes, both tubular and vascular, within the renal medulla. Recently, there have emerged differing hypotheses about the renal tubular processes responsible for maintaining a hypertonic medullary interstitium. In this Editorial Review, R.W. Berliner frames three questions germane to this issue, and J.P. Kokko and D.J. Marsh provide their responses to these queries. The major issues addressed are: 1) What are the major unresolved question(s) concerning the mechanism by which concentrated urine is formed? 2) Current evidence suggests that the urea concentration in thin ascending limbs is slightly lower in the lumen than in interstitial fluid. Is the transepithelial concentration gradient between thin ascending limb and renal medullary interstitium sufficient to permit an entirely passive mechanism for diluting tubular fluid in the thin ascending limb? 3) A simple three-compartment model for the renal medullary concentrating process would include the tubular lumen, peritubular capillary, and the interstitium. Is it possible to generate a model that, by juxtaposing medullary structures, might explain renal medullary counterflow processes more adequately than the simple three-compartment model?

In physiological salt solution (PSS) which mimicks the cardiac cells cytoplasm and contains 120 mM K-MES, 10 mM NaCl, 20 mM imidazole, pH 7.2, 20 mM taurine, 15 mM creatine, 15 mM Na2phosphocreatine, 5 mM Na2ATP, 8 mM MgCl2, 5 mM K2HPO4, 3 mM glutamate, 3 mM malate, 0.5 mM dithiothreitol and 10 mg/ml of bovine serum albumine both isolated mitochondria and intracellular structures in skinned fibers stay intact. In PSS mitochondrial creatine kinase remains firmly attached to the inner membrane surface. CKmi-mi is extracted from cardiac mitoplasts in 0.125 M KCl solution, but addition of 10 mM sodium borate to this KCl solution completely inhibits dissociation of CKmi-mi. Therefore, not ionic strength but ion composition is important for association of CKmi-mi with mitochondrial membrane. Functional and structural studies using antibodies against CKmi-mi showed that in PSS CKmi-mi is bound to the inner mitochondrial membrane in spatially close relationship to adenine nucleotide translocase (ANT). Thus, under physiological conditions CKmi-mi is structurally and functionally coupled to ANT in cardiac mitochondria and functions to catalyze almost complete utilization of mitochondrial ATP for aerobic phosphocreatine synthesis.

The effects of mefenamic acid on the food-induced changes in intestinal carbohydrate metabolism were determined in an attempt to elucidate the mechanism(s) by which inhibition of prostaglandin synthesis enhances the postprandial increases in intestinal blood flow and oxygen consumption. The data show that when the luminal perfusate was changed from saline to a nutrient/bile solution, there was an increase in carbohydrate utilization, which was offset by absorption of glucose from the lumen. Intravenous administration of mefenamic acid significantly increased both carbohydrate absorption and metabolism when food was placed in the lumen. Changes in carbohydrate absorption and metabolism have been shown to play and important role in determining the magnitude of glucose induced changes in intestinal blood flow and oxygen consumption. Therefore, it is possible that the ability of mefenamic acid to enhance significantly the food-induced increases in blood flow and oxygen consumption may be due in part to its effects on intestinal carbohydrate absorption and utilization.

Is the NaCl signal perceived as a small increase in the concentration of NaCl in extracellular fluid? We used 8 g NaCl/100 g soluble nutrients and fed only a hypertonic (1.4% NaCl) or a hypotonic (0.45% NaCl) drink to Dahl salt-sensitive (DS) rats. After 12 weeks, 11 rats receiving the hypertonic drink had a mean blood pressure of 195 mm Hg versus 195 mm Hg in 12 rats receiving the hypotonic drink. Thus, the high-NaCl signal seems unrelated to a higher NaCl concentration in extracellular fluid, thereby suggesting volume signals. Most volume controls are near the third brain ventricle (3V). As a working hypothesis, high dietary NaCl may swell the tissues surrounding 3V, which is slitlike. Such swelling would partially close the upper part of the slit and cause ependymal cells and nerve fibers on opposite walls to touch, possibly leading to hypertension in susceptible humans or rats. To test this, we stereotaxically blocked the aqueduct with inert silicone to produce hydrocephalus of 3V in DS rats and thus prevent ependymal cells and nerve fibers from touching. After blocking or sham-blocking the aqueduct, either a 6% NaCl diet or a 0.23% NaCl diet was started. Intra-arterial blood pressure was taken after 6 weeks. A group of 28 sham-blocked rats and a group of 29 blocked rats, all fed a 0.23% low NaCl diet, had equal blood pressures averaging 130 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

An in vitro method has been used to examine whether secretion of renin from the juxtaglomerular apparatus is affected by changes in the sodium chloride concentration of the tubular fluid at the macula densa. Single juxtaglomerular apparatuses were microdissected from rabbits and the tubule segment containing the macula densa was perfused, while simultaneously the entire juxtaglomerular apparatus was superfused, and the fluid was collected for renin measurement. In this preparation, in which influences from renal nerves and local hemodynamic effects are eliminated, a decrease in the tubular sodium chloride concentration at the macula densa results in a prompt stimulation of the renin release rate.

The phenotypic difference between virulent and avirulent Legionella pneumophila with regard to growth on supplemented Mueller-Hinton (SMH) agar was investigated. Defined populations of virulent and avirulent L. pneumophila were inoculated onto hybrid growth media containing the combination of SMH agar components with potassium phosphate-buffered charcoal-yeast extract agar. The casein acid hydrolysate component of SMH agar was found to be inhibitory to the growth of virulent but not avirulent cells. The selectively inhibitory component of the casein acid hydrolysate was identified as NaCl.

Dahl salt-sensitive (S) rats which are susceptible to hypertension have lower urinary kallikrein excretion than salt-resistant (R) rats which are not susceptible. Some physicochemical characteristics of partially purified urinary kallikrein were compared between the S and R strains. The isoelectric focusing pattern of S kallikrein was shifted so that a higher proportion of enzyme was present in isoelectric forms that had higher pI values compared to the pattern for R kallikrein. This strain difference was unique to urinary kallikrein; it was not seen in kallikrein extracted from salivary glands. The isoelectric focusing pattern for R urinary kallikrein could be converted to an S-type pattern by treatment with neuraminidase, which suggests that the differing isoelectric focusing patterns arose from differences in the sialic acid content of the kallikrein. The S kallikrein was slightly more heat-labile than R kallikrein, which was also compatible with the lower sialic acid content of the S enzyme. Tests involving the active site of the enzyme (Km values, pH curves, and heat of activation) were identical for the S and R strains. It was concluded that the structural differences observed in urinary kallikrein between S and R strains were compatible with strain-specific posttranslational processing of the enzyme.

The control of gastric emptying has been restudied. Methods used are described. It was found that in the alert unanesthetized monkey saline is emptied from the stomach at a rate that is volume-dependent; an exponential curve results since higher volumes provoke more rapid emptying and lower volumes slower emptying. For glucose test meals emptying is quite linear; also emptying is slower and progressively slower with progressive increases in glucose concentration. There is, however, an early rapid phase of gastric emptying that converts to a slower, more linear pattern. Calories rather than osmoles appear to control emptying. Glucose in the pyloris has an inhibitory effect in gastric emptying. A theory of control is discussed. The control of gastric emptying also relates to the control of feeding.

This study was designed to determine whether cholecystokinin (CCK) plays a physiological role in the inhibition of gastric emptying. Physiological conditions were simulated by giving CCK by continuous intravenous infusion rather than by bolus injection, by using doses known to be distinctly submaximal for pancreatic protein secretion, and for gallbladder contraction, and by releasing endogenous CCK. The rate of gastric emptying was determined in 4 dogs with gastric fistulas by measuring the volume of fluid remaining in the stomach 10 min after instillation of 300 ml of 0.15 M NaCl. Rate of emptying was studied during intravenous infusion of saline (control) and of different doses of 98% pure CCK, commerically available 20% pure CCK, synthetic COOH-terminal octapeptide of CCK (OP-CCK), pentagastrin, and heptadecapeptide gastrin. The effect of endogenously released CCK was studied by measuring the rate of emptying of solutions in which different concentrations of tryptophan replaced equiosmolar amounts of NaCl. The d50's of 20% pure CCK (3 U kg minus-1 hr minus-1) and of OP-CCK (125 ng kg minus-1 hr minus-1) for inhibition of gastric emptying were about the same as their D50's for cholecystokinetic and pancreozyminic actions. By contrast, although both pentagastrin and heptadecapeptide gastrin inhibited gastric emptying, the doses required for this action were much higher than the D50's required for stimulation of gastric acid secretion. The effectiveness of OP-CCK indicates that inhibition of gastric emptying is attributable to CCK itself and not to an impurity in the CCK preparation. We have confirmed this directly by showing that pure CCK is a potent inhibitor of gastric emptying. Tryptophan also inhibited gastric emptying. In other dogs pancreatic protein secretion and gallbladder contraction were shown to be stimulated during the time tryptophan was inhibiting gastric emptying. This evidence supports the view that inhibition of gastric emptying is one of the physiological actions of CCK, but in the case of gastrin it must be regarded as a pharmacological action.

Behavioral and electrophysiological experiments were performed to examine whether or not the taste of 'umami' substances such as monosodium glutamate (MSG), disodium 5'-inosinate (IMP), and disodium 5'-guanilate (GMP) is really unique in hamsters. When the animals were conditioned to avoid ingestion of MSG (or IMP) or their mixture by pairing its ingestion with an i.p. injection of LiCl, suppression of drinking generalized to IMP (or MSG), GMP, NaCl, and other sodium salts. Suppression of drinking after conditioning to NaCl generalized to MSG, IMP, GMP, and inorganic sodium salts. These learned aversions to umami substances and sodium salts were abolished by bilateral deafferentation of the chorda tympani, but were not affected by destruction of the bilateral glossopharyngeal nerves. The integrated whole-nerve responses of the chorda tympani to MSG, IMP, and NaCl were similar to each other, consisting of the initial dynamic phase and the following tonic phase. Synergism of chorda tympani responses to a mixture of MSG and IMP was not observed. Across-fiber response patterns of the chorda tympani for MSG, IMP, or their mixture were very similar to that for NaCl. Even the high concentrations of umami substances (0.3 M MSG, 0.3 M IMP, and the mixture) did not elicit any detectable responses in the glossopharyngeal nerve. These results suggest that the taste of umami substances is not unique in the hamster, but is similar to that of sodium salts, and is mediated exclusively via the chorda tympani.

Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

The absorption of fluid by epithelial tissues is thought to be due to the existence of hypertonic regions within the epithelium. The magnitude of the required hypertonicity as well as its localization have been the subject of considerable experimental and theoretical effort. Model calculations demonstrated the need for knowledge of the water permeability of the membranes of epithelial cells for the purpose of estimation of the osmotic gradients required for fluid absorption. We measured the hydraulic water permeability of the individual cell membranes of Necturus gallbladder by quantitative light microscopy. The water permeabilities were sufficiently high so that small osmotic gradients were required to achieve normal rates of fluid transport. The cell osmolality was calculated to exceed that of the mucosal bathing solution by about 2 mosmol kg-1, and the basolateral interstitial osmolality was calculated to be about 1 mosmol kg-1 greater than that of the cell. The fluid absorbed by the epithelium must be slightly hypertonic to the bathing solutions. Knowledge of the apical cell membrane water permeability and the relative area of the cell and tight junction allow a calculation of the relative flow of fluid across both pathways. It can be readily shown that osmotically induced flow across the epithelium occurs predominantly transcellularly because of the small area of the junctional pathway and the high water permeability of the cell membranes.

The involvement of chemotherapy stimuli in the feeding behavior of the blood-sucking leech Hirudo medicinalis was investigated using a behavioral feeding test in which test solutions were encased in a highly permeable membrane and presented to the leech. Whole human blood or plasma at ambient temperature elicited the complete sequence of feeding behavior: probing, attachment, biting and ingestion. Spring water, 300 mM sucrose, or dialyzed plasma did not elicit any of these responses. Spring water warmed to 38 degrees C elicited probing and transient attachment but not ingestion. Thus, appropriate chemical stimuli were necessary for complete feeding behavior. A chemically defined artificial blood mix, containing the major components of low molecular weight found in blood, elicited all aspects of leech feeding behavior. Eliminating either NaCl or arginine from the mix resulted in complete loss of effectiveness. Moreover, a solution containing only NaCl (150 mM) and arginine (90 microM) was also an effective feeding stimulus. Thus, appropriate chemical stimuli are sufficient for complete feeding behavior. Neither NaCl nor arginine alone induced feeding although NaCl alone elicited probing. Sensory detection of blood was localized to a region of the dorsal lip that contains structures composed of ciliated, bipolar neurons, which are likely candidates as chemoreceptors. Surgical ablation of this region of the skin resulted in complete loss of ability to alert to, orient toward and ingest blood, while sham-operated controls fed normally. Substitution with other ions revealed specificity, with respect to both the cation and the anion, in the response to NaCl. Of the inorganic and organic cations tested, only Li+ substituted effectively for Na+. Of the inorganic and organic anions tested, only Br- was as effective as Cl-. Thus, the requirement for NaCl in leech feeding represents more than simply an ionic strength requirement or a requirement for Na+ ions and bears similarities to the chemosensory detection of NaCl in other species. Substitution with other amino acids and analogues for arginine revealed marked specificity in the feeding response to this compound as well. D-arginine at concentrations of up to 1000-fold greater than the effective threshold for L-arginine did not elicit ingestion, nor did other common L-amino acids, including the other basic amino acids histidine and lysine. Of the arginine analogues tested, only homoarginine and canavanine (in which all three functional groups of arginine are unchanged) were effective feeding stimulants.

We have studied the effects of the anthracycline doxorubicin on the release of catecholamines from the perfused bovine adrenal gland. Doxorubicin produced different concentration-dependent effects on adrenomedullary catecholamine secretion. At a 3 x 10(-6) M concentration, doxorubicin facilitated the secretory response induced by acetylcholine and 56 mM K+ but did not affect the spontaneous catecholamine output or that evoked by NaCl deprivation. Conversely, a higher concentration of doxorubicin (10(-4) M) resulted in a significant and irreversible inhibition of the spontaneous secretion of catecholamines, as well as of that caused by acetylcholine or high K+. Doxorubicin at this high concentration did not modify the catecholamine release induced by NaCl deprivation. These results suggest that doxorubicin effects could be mediated at the plasma membrane of the chromaffin cells. The present study is compatible with the idea that increased adrenomedullary catecholamine release is involved in the cardiotoxic action of relatively low doses of doxorubicin.

The effects of sodium deprivation for 10 d, a period sufficient to induce sodium appetite, on gustatory nerve discharges in rats were determined. Chorda tympani responses to concentration series of sodium chloride, sucrose, hydrochloric acid, and quinine hydrochloride were recorded and analyzed without the experimenter knowing the animal's deprivation condition. After deprivation, both whole nerve and single nerve fiber responses to sodium chloride were smaller; NaCl-best fibers, those more responsive to sodium chloride than to sucrose, hydrochloric acid, or quinine, were most affected. Thresholds had not changed; however, slopes of the stimulus-response functions for sodium chloride were lowered. Comparable changes in responses to the other stimuli did not occur. These results were discussed with respect to a possible relationship between changes in sodium chloride responsivity and changes in sodium intake, differences between methods of inducing sodium appetite, coding of taste quality and intensity, and mechanisms which might effect the responsivity change.

The effect of a salt supplemented diet on the voluntary intake of ethanol in male Wistar rats was examined in two experiments. In Experiment 1, the addition of 3% sodium chloride to the diet selectively increased the intake of moderately concentrated ethanol solutions (3 and 6%) while leaving the choice of a 12% solution unaffected. The choice and intake of water in the two former groups declined. In a second experiment four different groups of rats were offered the 3% salt supplemented diet in combination with daily injections of the synthetic salt-retaining mineralocorticoid desoxycorticosterone acetate (0.5, 1.5, and 6.0 mg/day). Ethanol intake again tended to increase in the 3 and 6% groups but in contrast to the results of Experiment 1 water intake also increased significantly. When desoxycorticosterone was administered without the salt supplemented diet, ethanol intake was significantly depressed while water intake increased. These findings indicate that a salt supplemented diet can significantly and selectively enhance the intake of moderately concentrated ethanol solutions and that while the addition of desoxycorticosterone injections to this diet has its effect primarily on water intake, these injections alone can also suppress ethanol intake indirectly by shifting the animals choice toward water and away from ethanol.

Various studies point to a role of the renal prostaglandin (PG) system in the regulation of renal NaCl excretion. In the present experiments, distal delivery of proximal tubular fluid (DD) [CH20 + CC1)/GFR x 100] and distal fractional chloride absorption (DFAC1) [CH20/(CH20 + CC1)] were studied in 6 healthy volunteers undergoing sustained water diuresis. Studies of renal function were performed during intravenous infusion of hypotonic (0.45%) saline and during additional treatment with indomethacin, furosemide and furosemide plus indomethacin. Hypotonic saline was infused at increasing rates of 0.09, 0.18, and 0.36 ml min-1 kg-1 body weight each for a 45-min period. DD over all three clearance periods averaged 8.27 +/- 0.71 ml min-1 100 ml-1 glomerular filtration rate (GFR) during saline infusion alone and was unchanged by indomethacin (8.09 +/- 0.63 ml min-1 100 ml-1 GFR). DFAC1 averaged 0.79 +/- 0.02 during saline and significantly increased to 0.87 +/- 0.01 (p less than 0.002) during concomitant indomethacin treatment. Increased NaCl absorption in the diluting segment during indomethacin was paralleled by a decrease in urinary excretion of chloride (UC1V) from 221 +/- 29 during control to 124 +/- 19 muEq/min (p less than 0.025) and in urinary excretion of PGE2 (UPGE2V) from 1.45 +/- 0.12 to 0.51 +/- 0.09 pmol/min (p less than 0.025). Furosemide increased UPGE2V to 2.94 +/- 0.34 pmol/min (p less than 0.05) and UC1V to 2,590 +/- 128 muEq/min (p less than 0.001). This effect was associated with an increase in DD to 26.70 +/- 1.33 ml min-1 100 ml-1 GFR (p less than 0.001) and a decrease in DFAC1 to 0.19 +/- 0.02 (p less than 0.001). Neither DD and DFAC1 nor UC1V were altered during furosemide+indomethacin as compared to furosemide in spite of a marked suppression of UPGE2V to 0.56 +/- 0.13 pmol/min. Our results support the concept that renal PG participate in the regulation of NaCl absorption in the diluting segments of the nephron. Furthermore, the tubular effects of furosemide appear not to be mediated by the PG system.

In Study A, rats were implanted with a cannula aimed at either the lateral (LV) or ventral third (V3V) brain ventricles 1 week prior to starting a chronic oral regimen of captopril. The presence of neither cannula significantly impaired the emergence of captopril-induced appetite for NaCl solution. In Study B, V3V cannulae were implanted in rats after a captopril-induced appetite for NaCl was established. The surgery produced a 1-2 day attenuation of NaCl intake, but this was no greater than that observed in a sham-operated group that received no cannula. These results do not support those of others who suggest that captopril (and, by inference, other agents) can leak across a damaged blood-brain barrier for at least 2 weeks after placement of a cannula. Possible reasons for the differences in results are addressed.

The mode of water flow in the Tenon's capsule and the subconjunctival tissue was studied in the rabbit. Carbon-black ink injected under the Tenon's capsule was found to move along the plane of the capsule posteriorly toward the optic nerve sheath and also along the direction of the corneal limbus, but a very little amount moved through the layers of the capsule. The flow rates of physiological saline through the capsule were determined under various hydrostatic pressures, and the water flow conductivity through the capsule averaged 8.8 +/- 5.5 X 10(-12) cm4 dyne-1 sec-1 in 7 eyes. The Tenon's capsule offered a considerable resistance to water flow through its layers. The upper conjunctiva was dissected to the limbus and the wound was closed 1) after subconjunctival injection of saline and 2) after injection of concentrated sodium hyaluronate. One month later, a needle connected to a saline reservoir was inserted into the subconjunctival tissue of the treated area and the rate of water flow into the tissue was determined under various hydrostatic pressures. The results were compared with those in the normal eye. The water flow rate was significantly less in the treated eye than in the normal eye. The eyes treated with sodium hyaluronate tended to show a higher flow rate than those treated with saline. Histological examinations revealed that an intensive scar formation took place in the dissected area, indicating that scar formation greatly reduces water flow in the Tenon's capsule and subconjunctival tissue.

Proton and formic acid permeabilities were measured in the in vivo microperfused rat proximal convoluted tubule by examining the effect on intracellular pH when [H] and/or [formic acid] were rapidly changed in the luminal or peritubular fluids. Apical and basolateral membrane H permeabilities were 0.52 +/- 0.07 and 0.67 +/- 0.18 cm/s, respectively. Using these permeabilities we calculate that proton backleak from the luminal fluid to cell does not contribute significantly to net proton secretion in the early proximal tubule, but may contribute in the late proximal tubule. Apical and basolateral membrane formic acid permeabilities measured at extracellular pH 6.62 were 4.6 +/- 0.5 X 10(-2) and 6.8 +/- 1.5 X 10(-2) cm/s, respectively. Control studies demonstrated that the formic acid permeabilities were not underestimated by either the simultaneous movement of formate into the cell or the efflux of formic acid across the opposite membrane. The measured apical membrane formic acid permeability is too small to support all of transcellular NaCl absorption in the rat by a mechanism that involves Na/H-Cl/formate transporters operating in parallel with formic acid nonionic diffusion.

Regulation of taurine transport and accumulation in explanted fetal mouse hearts is shown to be under osmotic control. All osmotic agents studied, both ionic (NaCl, LiCl, choline Cl) and nonionic (sucrose, glucose) stimulated [3H]-taurine transport during an incubation of 19 h. Hyperosmotic stimulation of transport achieved statistical significance by 3 h in the presence of sucrose (P less than 0.05). After 1 h, 40 mM NaCl engendered a 56% increase in [3H]-taurine transport (P less than 0.01). The NaCl stimulation at 1 h may relate more to the transport system's absolute sodium ion requirement than hyperosmotic stimulation. Incremental addition of NaCl or sucrose linearly stimulates [3H]-taurine transport in an incubation of 19 h. Total taurine, measured by HPLC, increased 25% with addition of either 40 mM NaCl or 80 mM sucrose. Hyperosmotic stimulation of transport was not blocked with propranolol but was additive to beta-adrenergic stimulation of transport. Osmotic stimulation occurred with a large increase in Vmax (0.41----0.81 nmol/mg tissue/h) but only a small change in Km (0.51----0.43 mM). After 1 h preincubation with a hyperosmotic addition phenylalanine transport was measured, but was not different from control. Phenylalanine accumulation measured during 19 h incubation similarly was not altered. Streptozotocin induced diabetic rats had elevated plasma osmolarities (295 +/- 2.1----322 +/- 1.3 mosmol) and cardiac taurine (24.3 +/- 1.2----36 +/- 1.0 mumol/g wet wt.). The data presented demonstrates that mammalian cardiac taurine is regulated by the osmotic environment of the heart, suggesting an osmoregulatory function for intracellular taurine and physiological relevance in disease states such as diabetes.