Sodium Output Research Articles

Does aggressive hydration reverse the effects of pneumoperitoneum on renal perfusion?

Although pneumoperitoneum (PP) decreases renal blood flow, it remains unclear whether this impacts renal function. Our aim was to characterize the effects of PP on renal perfusion and function using two fluid strategies for intravenous fluid administration. Twelve 30-kg pigs were randomized into two groups: maintenance (3 cc/kg/h of normal saline (NS)) and bolus (15 cc/kg/h + 20 cc/kg NaCl bolus prior to induction of PP). Pigs were studied in a blinded fashion for 30 min prior, 60 min during, and 30 min after release of 15 mmHg CO(2) PP. Cardiac output (CO) and stroke volume (SV) were measured using an esophageal Doppler probe, renal cortical perfusion (RCP) was measured with a laser Doppler probe on the right kidney, and renal function was measured using the fractional excretion of sodium (FeNa) and urine output. Statistical analysis was performed with area-under-the-curve (AUC) analysis and analysis of variance AUC analysis revealed moderate effect size for CO (0.416) and small effect size for SV (0.366) and RCP (0.363), with decreases seen in the control group but not the bolus group. During PP, urine output increased in the bolus group (p = 0.04) but not in the control group; there was no difference in FeNa in either group. Aggressive fluid hydration during CO(2) PP of 15 mmHg preserves CO, SV, and RCP while increasing urine output. No effect on renal function as measured by FeNa was observed in either group.

Absorption from the jejunum is increased by forward and backward pacing.

In 4 dogs a 75-cm segment of jejunum was isolated from the intestinal stream. Stimulating electrodes were implanted at each end of the segment and recording electrodes at intervals between. The two ends of the segment were fashioned as stomas on the anterior abdominal wall. After recovery, the electrical activity of the segment was continuously recorded, whilst a solution of 100 mmol/l glucose and 90 mmol/l NaCl was infused into the proximal stoma at 2.9 ml/min. Effluent from the distal stoma was collected in 5-min aliquots for three consecutive 30-min periods. In the second period electrical stimuli were given via either the proximal or the distal bipolar electrodes to entrain pacesetter potentials. Both forward and backward electrical pacing decreased the output of water, glucose and sodium from the jejunal segment, but the decrease was significantly greater with backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli produces a greater increase in absorption from the segment than pacing it forwards, a finding which has therapeutic implications in patients with the short bowel syndrome.

Cause and management of high volume output salt-depleting ileostomy

Ileostomy function was studied in 12 patients with an established ileostomy following proctocolectomy, in 6 of whom minimal amounts (less than 9 cm) and in 6 significant amounts (30-120 cm, mean 60 cm) of terminal ileum had been removed. Patients who had undergone significant ileal resection had daily faecal volumes considerably greater than those with minimal ileal resection (1202 +/- 284 ml versus 401 +/- 92 ml, P less than 0.001), and also greater daily outputs of sodium (146 +/- 53 mEq versus 43 +/- 12 mEq) and potassium (12.7 +/- 9.0 mEq versus 4.0 +/- 0.99 mEq). The percentage water content of the ileostomy fluid was greater in patients who had had the ileum resected (93.1 +/- 1.8% versus 89.8 +/- 2.5%). In addition, the sodium/potassium ratio in the urine in patients with a properly acting ileostomy after ileal resection was low. It is concluded that when recurrent inflammatory bowel disease, partial small bowel obstruction and intraperitoneal sepsis have been excluded there remains a number of patients whose high ileostomy output is due entirely to the amount of ileum resected. The management of patients with a high output ileostomy with codeine phosphate, Lomotil and oral administration of sodium chloride tablets is discussed.

Effects Of Preexercise Rehydration Beverages On Fluid Balance And Exercise Tolerance

Decreases in plasma and intracellular water volumes during exercise may decrease sweat rate, promote hyperthermia, and increase the rate of glycogen utilization. Rehydration beverages containing electrolytes and carbohydrates may increase water intake during exercise and limit water excretion in urine. PURPOSE To study the efficacy of 4 preexercise beverages on fluid balance during submaximal exercise and subsequent exercise performance. METHODS Twenty healthy people (10 male, 10 female; 24±3 y) exercised at 57±4% (mean±SD) VO peak in a thermoneutral environment (WBGT= 16.2±1.6 °C) for 90 min, 45 min after ingesting 355 ml of either chicken noodle soup (SOUP), a carbohydrate/electrolyte beverage (CE), or water (WATER). Water intake during exercise was allowed ad libitum except in a second soup trial (SOUPCON) where water was given at times and volumes equal to CE. After 90 min of steady state exercise subjects performed a time trial in which they accumulated as rapidly as possible the amount of work equal to 30 min at ∼60% VO2peak. Results: Total body mass lost and urine output were similar between trials. The additional water ingested during SOUP, CE, and SOUPCON (p<0.01) compared to WATER resulted in enhanced fluid balance in SOUP and SOUPCON compared to WATER and CE (−268±414 g and −328±500 g vs. −654±577 g and −477±596 g respectively, p<0.05). The percent change in plasma volume was not different in any trial. Plasma sodium was similar in all trials (p=0.8). Plasma osmolality (p=0.01) was higher during SOUPCON compared to CE and WATER at before and during exercise (P<0.05) and was higher in SOUP compared to WATER and CE at the end of exercise (p<0.05). Urine specific gravity increased in CE, WATER, and SOUPCON (p<0.05 for all). Urine osmolality decreased in CE and increased in SOUPCON (p<0.05), and total urinary output of sodium and potassium was higher in SOUPCON compared to CE (p<0.05). Heart rate, systolic and diastolic blood pressures, rectal temperature, and thirst responses were not different between trials. No performance differences were observed in the time trial (p=0.4). CONCLUSIONS Higher electrolyte concentrations associated with chicken noodle soup (S and SOUPCON) resulted in better maintenance of fluid balance due to increased water intake and less urinary water loss. Fluid balance differences did not result in significant differences in percent plasma volume, heart rate, blood pressure, body temperature regulation, or subsequent exercise performance. Supported Campbell Soup Co, Inc.

Parathyroid hormone and rates of bone formation are raised in perimenopausal rural Gambian women

To investigate rates of bone turnover and calcium homeostasis in Gambian women, we recruited 103 peri- and postmenopausal women, aged 45 to 80+ years and 11 women of reproductive age. Fasting blood was analyzed for plasma osteocalcin, PTH, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], total- and bone-specific alkaline phosphatase. Plasma and urinary calcium, inorganic phosphate, sodium, potassium, creatinine, and albumin and urine free deoxypyridinoline (Dpd) was also measured. Samples from 20 premenopausal and 31 postmenopausal women from Cambridge, UK were analyzed, using the same methodology for comparison.For the Gambian women, peak calcium excretion occurred at around 50 years of age. For women aged ≥45 years, calcium excretion decreased by 3.0% per year of age (SE 1%; P < 0.005). In this age group, 25(OH)D also decreased with age (P < 0.005). Urinary sodium output, pH, and titratable acid output decreased (all P < 0.05) and total alkaline phosphatase (P < 0.005), osteocalcin (P < 0.005), and PTH (P < 0.05) increased with age.Comparisons were made between the following groups of Gambian and British women: premenopausal, early (age 55–64 years)- and late (age 65+ years)-postmenopausal. Gambian women of all ages were lighter (P < 0.001), shorter (P < 0.01), and had higher plasma bone-specific alkaline phosphatase activity (P < 0.05) and higher concentrations of osteocalcin (P < 0.05), PTH (P < 0.001), 1,25(OH)2D (P < 0.001), and 25(OH)D (P < 0.001). There were no consistent differences in calcitonin, while urinary free Dpd outputs were lower in the Gambians (P < 0.001). Plasma calcium, phosphate, and albumin (P < 0.01) were significantly lower. Urinary calcium, phosphate, sodium, and potassium excretion were lower, particularly in the postmenopausal group (P < 0.001). Although Gambian urine pH was more acidic, titratable acid output was lower (P < 0.01).These data show that Gambian women with low dietary calcium intakes and good vitamin D status have low urinary calcium excretion and that menopausal changes in calcium and bone metabolism among Gambian women are similar to those seen in other populations.In addition, they demonstrate that Gambian women of all ages have raised plasma PTH and 1,25(OH)2D concentrations and raised markers of osteoblast activity. We postulate that high endogenous PTH concentrations may be beneficial to bone health in Gambian women, removing fatigue damage and improving bone quality.

Dietary habits and nutritional biomarkers in Italian type 1 diabetes families: evidence of unhealthy diet and combined-vitamin-deficient intakes.

Nutritional status and lifestyle can have profound effects on health. To analyse behaviour patterns in population subgroups of public health importance, we compared lifestyle, dietary intake of energy and selected nutrients, and nutritional biomarkers of type 1 diabetes (T1DM) patients and nondiabetic first-degree relatives against control subjects with no family history of T1DM. A cross-sectional study. Department of Internal Medicine, University of Pisa, Italy. A total of 209 individuals including 38 type 1 patients, 76 relatives, and 95 healthy subjects. We used the European Prospective Investigation of Cancer and Nutrition questionnaires to assess dietary intake and lifestyle. Anthropometric indices and nutritional biomarkers (such as plasma levels of albumin, iron, lipids, homocysteine, vitamin B9 and vitamin B12 as well as urinary outputs of nitrogen, sodium and potassium) were evaluated. Emerging health issues: (1) In total, 45% of controls were overweight. Increasing age was associated with increasing body mass and decreasing activity in sport in front of an unchanged energy intake. (2) The distribution of energy sources was incorrect. The proportion of caloric intake derived from total fat and cholesterol did not match general guidelines. Total dietary fibre consumption was assessed to be adequate (25 g/day) in only 27% of all the participants. (3) Estimated daily intakes of water-soluble vitamin B9 and fat-soluble vitamin D and vitamin E were deficient in comparison with dietary reference intakes. (4) The prevalence of adoption and maintenance of healthful eating and physical activity habits was higher in women and T1DM patients (probably as a consequence of the medical educational intervention). On the contrary, supportiveness of the family in term of changing the undesirable behaviours at home seemed to fail. This study provides first evidence indicating unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. The combination of vitamin B9 and vitamin E deprivation could be deleterious for endothelial function, since these antioxidants have been implicated in the modulation of nitric oxide and eicosanoid signalling.

Circadian renal rhythms influenced by implanted encapsulated hANP-producing cells in Goldblatt hypertensive rats.

Renal excretion in experimental hypertensive rats implanted with encapsulated human atrial natriuretic peptide (hANP)-producing cells is circadian periodic. Chinese hamster ovary (CHO) cells transfected with the plasmid hANP-cDNA were encapsulated in biocompatible polycaprolactone capsules for intraperitoneal implantation into two-kidney, one-clip (2K1C) hypertensive rats. During a 12:12 light-dark cycle, as compared to control CHO cells, the implantation of encapsulated hANP-producing CHO cells was associated with an increase in the net excretion of water, sodium and potassium, and with a reversal of the advanced circadian phases related to renovascular hypertension in 2K1C rats. The increase in blood pressure postimplantation was delayed, and increases in renal blood flow, glomerular filtration rate, sodium output, urinary excretion and urinary cyclic GMP concentrations were also found. Implantation of encapsulated hANP-producing cells affects circadian rhythms in kidney excretion functions of 2K1C rats, and may be useful for the treatment of cardiovascular disease.

English translation of abstracts of original articles published in German 50 years ago on the discovery of aldosterone

Chemical degradation of the new crystalline mineralocorticoid provisionally called electrocortin has shown that this compound is 11h,21-dihydroxy-3,20-diketo-4-pregnen18-al. In solution, this reacts mainly as the 11-hemiacetal. We suggest aldosterone as the definitive name for the compound. Simpson SA, Tait JF, Wettstein A, Neher R, von Euw J, Schindler O, Reichstein, T. Aldosteron, Isolierung und 0167-5273/$ see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2004.05.005 * Corresponding author. Tel.: +44 113 392 5401; fax: +44 113 392 5395. Eigenschaften. Ueber Bestandteile der Nebennierenrinde und verwandte Stoffe. 91. Mitteilung. Helv. Chim. Acta 1954;37:1163–200. Title: Aldosterone. Isolation and characteristics. The constituents of the adrenal cortex and related substances. Abstract: We previously described, in two brief reports, the isolation and chemical structure of a new crystalline corticoid with a particularly potent effect on mineralocorticoid metabolism. The hormone was provisionally called electrocortin. After identification of its chemical structure the name aldosterone was suggested as the definitive name, which is in keeping with the internationally accepted nomenclature classification. In the mean time, the same substance has also been isolated in crystalline form by Mattox and co-workers. We report here the details of its chemical structure, isolation and its characteristics. We previously described, in two brief reports, the isolation and chemical structure of a new crystalline corticoid with a particularly potent effect on mineralocorticoid metabolism. The hormone was provisionally called electrocortin. After identification of its chemical structure the name aldosterone was suggested as the definitive name, which is in keeping with the internationally accepted nomenclature classification. In the mean time, the same substance has also been isolated in crystalline form by Mattox and co-workers. We report here the details of its chemical structure, isolation and its characteristics. Simpson SA, Tait JF, Wettstein A, Neher R, von Euw J, Schindler O, Reichstein, T. Die Konstitution des Aldosterons. Ueber Bestandteile der Nebennierenrinde und verwandte Stoffe. 92. Mitteilung. Helv. Chim. Acta 1954;37:1200–23. Title: The chemical structure of aldosterone. Constituents of the adrenal cortex and related substances. Abstract: We previously described, in two brief reports, the isolation and chemical structure of aldosterone. Details ology 96 (2004) 497–498 We previously described, in two brief reports, the isolation and chemical structure of aldosterone. Details ology 96 (2004) 497–498 D. Schlosshan et al. / International Journal of Cardiology 96 (2004) 497–498 498 regarding its isolation and the characteristics and derivatives of this hormone were described in the 91st report of this series. Here, we would like to report the results of the identification of its chemical structure. Chemical degradation of aldosterone has shown that this compound is an 18oxo-corticosterone. In solution, it probably can be found predominantly in the cyclohemiacetal form. Simpson SA, Tait JF, Wettstein A, Neher R, von Euw J, Reichstein, T. Isolierung eines neuen kristallisierten Hormons aus Nebennieren mit besonders hoher Wirksamkeit auf den Mineralstoffwechsel. Experientia 1953:9;333–5. Title: Isolation of a new crystalline hormone from the adrenal gland with a particularly potent effect on electrolyte metabolism. Recently, a new, highly sensitive method was described allowing rapid measurement of the effects of steroids on the ratio of urinary sodium and potassium output using only tracer amounts of substrate. With the help of this test, it was possible to demonstrate unequivocally that adrenal gland extracts indeed contain a specific substance with high activity that can also be detected after paper chromatographic separation and in the blood. It was also possible to purify this substance to a high degree. Using the method described above, the concentrates were 60–80 times more potent than cortexone. We have now been able to isolate this substance in a pure crystalline form from several concentrates prepared by our two research groups working in parallel in Basel. Methods and results: Extracts prepared from 500 kg of beef adrenals using the method described by Cartland and Kuizenga served as starting material. A total of 167 g of this material was purified using partition chromatography on large kiesleguhr columns with aqueous methanol:benzene solvent systems. Further purification using paper chromatography and repeated partition chromatography yielded 22 mg of the raw crystalline compound. Using the Na42/K42 method by Simpson and Tait, the compound described was around 100 times, and using the modified sodium retention method of Kagawa et al. around 50 times more potent than Cortexone. In (maintenance tests) in adrenalectomised dogs the compound appeared 30 times more potent than cortexone– acetate. Conclusion: We therefore consider that we have found a new important hormone of the adrenal cortex. We will report later about experiments leading to the chemical identification and synthesis of this compound as well as other more detailed biological experiments. We reserve the right to suggest a new name for the new compound at that time.

Effect of Dietary Corn Oil Supplementation on Equine Gastric Fluid Acid, Sodium, and Prostaglandin E2Content before and during Pentagastrin Infusion

The effect of corn oil (approximately 60% [wt/vol] linoleic acid) dietary supplementation on various components of equine gastric secretion was studied by use of a repeated‐measures experimental design. Four healthy adult ponies were surgically fitted with gastric cannulas. The ponies were then fed a free‐choice hay diet for 5 weeks, which was followed by 5 weeks of the same diet supplemented with 45 mL of corn oil daily. Gastric contents were analyzed under basal and pentagastrin‐stimulated conditions once weekly during the latter 2 weeks on each diet. Gastric contents were collected at 30‐minute intervals, and volume, hydrogen ion concentration, sodium content, and prostaglandin E2(PGE2) content were measured. Data were analyzed by a linear fixed‐effect modeling procedure. During the diet supplemented with corn oil, the ponies had, under basal and pentagastrin‐stimulated conditions, significantly decreased acid output and significantly increased PGE2and sodium outputs compared to those measured before corn oil supplementation. We conclude that corn oil supplementation may be an effective and inexpensive way to increase the protective properties of equine glandular gastric mucosa. This could be particularly helpful in reducing the chances of ulceration associated with nonsteroidal anti‐inflammatory drug (NSAID) administration.

Syndrome of inappropriate secretion of antidiuretic hormone and hyponatremia after spinal surgery.

Hyponatremia caused by an inappropriately high level of antidiuretic hormone secretion after spinal surgery is an uncommon and self-limiting phenomenon that resolves within 2 or 3 weeks. During the early postoperative period, the patient's urine output and serum level of sodium should be monitored closely to prevent possible serious complications of the syndrome of inappropriate secretion of antidiuretic hormone. Symptoms vary depending on the severity of the hyponatremia and can range from mild headache, muscle cramps, nausea, and vomiting to convulsions, coma, and death. Treatment options include fluid restriction, oral intake of salt, and hypertonic saline. It is important that spine surgeons recognize this phenomenon early and treat it appropriately and conservatively to prevent possible serious complications.

Effects of furosemide and bendroflumethiazide on saliva flow rate and composition

Aim of this study was to evaluate the effect on saliva flow rate and composition and on perceived xerostomia. The study used a Latin square design, all subjects being once daily (at 7.00 a.m.) taking the bendroflumethiazide (2.5 mg), furosemide (40 mg), or placebo, in a randomised order. Each treatment period of 7 days was separated by wash-out periods of 14 days. Unstimulated and paraffin chewing stimulated whole saliva, and 3% citric acid stimulated parotid and submandibular–sublingual secretion were collected twice daily, at 7.30 a.m., with the patients in a fasting condition (morning values), and at 10.30 a.m., about 2 h after intake of a standard breakfast (lunchtime values), on day 0 (baseline), day 1 (acute treatment), and day 7 (chronic treatment). Saliva flow rates were measured and all four secretions were analysed for the concentration of sodium, potassium, chloride, and total protein. Xerostomia was assessed by means of a Visual Analogue Scale. Statistical analysis used the Wilcoxon signed rank test. For flow rate, only that of submandibular–sublingual secretion was affected, significantly so in the morning during chronic treatment with both drugs. In resting whole saliva the output of both sodium and chloride tended to decrease especially during treatment with bendroflumethiazide, while in submandibular–sublingual secretion the output of all the electrolytes was decreased, especially for potassium and chloride and during treatment with furosemide. Further, xerostomia tended to increase during treatment with furosemide, statistically significant at lunchtime during chronic treatment. In conclusion, this study has demonstrated a modest effect on salivary flow rate and a more pronounced effect on saliva composition, especially in submandibular–sublingual secretion during treatment of healthy volunteers with therapeutic doses of two different diuretics, encouraging clinical studies in hypertensive patients and basic research as to the presence of a thiazide sensitive Na–Cl cotransporter in human salivary glands.

Encapsulated transgene cells attenuate hypertension, cardiac hypertrophy and enhance renal function in Goldblatt hypertensive rats.

The success of any gene-therapy approach depends on the survival of the genetically engineered cells that are implanted in the patient to deliver the therapeutic product. Immunoisolation of nonautologous cells within a microcapsule is a unique approach for gene therapy. We employed an immunoisolation device that protects nonautologous cells from destruction, to implant human atrial natriuretic peptide (hANP)-producing Chinese hamster ovary (CHO) cells in two-kidney, one-clip (2K1C) hypertensive rats. CHO cells transfected with the plasmid CMV-cANP were encapsulated in biocompatible polycaprolactone (PCL) capsules, and then the PCL capsules were implanted into 2K1C hypertensive rats intraperitoneally. The implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase 2 weeks post-implantation and the effect lasted for more than 5 months. The implantation of encapsulated hANP-producing cells also caused significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), sodium output, urine excretion, and urinary cGMP levels. These beneficial effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, reduction in cardiomyocyte size, tubular injury and renal arterial thickening. Immunoreactive hANP can be detected in the blood of 2K1C rats after implantation of the PCL capsules containing hANP-producing cells. This study demonstrates the usefulness of encapsulated ANP gene transfected cells as a new tool for ANP gene delivery in studying renovascular hypertension and cardiovascular diseases. Thus, our results may have important implications for clinical use of transgene cells as therapeutic agents in the treatment of cardiovascular diseases.

Effect of dietary salt restriction on tubular hypertrophy in rats with early‐stage chronic renal failure

Because salt restriction minimizes the occurrence of glomerular hypertrophy and tubular damage, we examined the effect of such restriction in rats with chronic renal failure (CRF). Male Sprague-Dawley rats were fed either a low-salt rat chow (65 mg sodium/100 g) or a normal salt diet (390 mg sodium/100 g) and underwent either 4/5 nephrectomy or a sham operation. Thus, there were four study groups (10 rats in each): a low-salt nephrectomy group (L-Nx); a normal diet nephrectomy group (N-Nx); a low-salt sham operation group (L-S); and a normal diet sham operation group (N-S). At the end of 8 weeks, all the rats were killed. Urinary sodium output, urinary protein excretion and blood pressure in L-Nx were significantly decreased in comparison to the values in N-Nx. Body weight, urine volume and glomerular filtration rate were similar between L-Nx and N-Nx. Histologically, the planar area of glomeruli and the smallest diameter of the proximal tubules in L-Nx were significantly reduced in comparison to those in N-Nx: 8.8+/-0.3 x 10(-3) vs 9.7+/-0.3 x 10(-3) mm2 (p < 0.01) and 6.7+/-0.1 x 10(-2) vs 7.4+/-0.1 x 10(-2) mm (p < 0.01). There were no statistically significant differences between L-S and N-S with the exception of urinary sodium output. Salt restriction in nephrectomized rats minimized the occurrence of proximal tubular hypertrophy independently of renal function. This suggests that salt restriction directly delays the occurrence of both tubular hypertrophy and glomerular hypertrophy in the presence of CRF.

Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats.

Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 microl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g). The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/ micro l) increased the urinary output of sodium (from 855.6 85.1 to 2055 310.6 delta%/min; N = 11) and potassium (from 460.4 100 to 669 60.8 delta%/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 micro g/3 micro l) administration (from 628 45.8 to 617 87.6 delta%/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 micro g/3 micro l) (from 498 +/- 39.4 to 517 +/- 73.2 delta%/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways.

Effects of lipopolysaccharide and phenylbutazone on gastric contents in the horse

Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species. That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS. The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 15 mins before a 60 min infusion of either LPS or saline. Gastric contents were collected at 15 min intervals for 3 h, beginning 15 mins after the start of the LPS or saline infusion. Lipopolysaccharide significantly decreased gastric acid output, [K+] and potassium output and increased [Na+] and sodium output. Phenylbutazone did not affect basal gastric acid secretion but decreased LPS-induced changes in the secreted volume, [Na+] and sodium output. This study provides evidence that LPS affects gastric acid secretion in the horse and that these LPS-induced changes are mediated, in part, by prostaglandins. Lipopolysaccharide administration can induce changes in the composition of gastric contents in the horse but further work is needed to determine the source of these changes.

Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects.

Regulation of body fluid homeostasis appears simple at first sight since daily sodium and water intake equals daily sodium and water output. The mechanisms enabling the body to excrete exactly the ingested and metabolically produced amounts of water and sodium are, however, complex and not completely understood. The factors regulating body fluid homeostasis may grossly be divided into humoral and physical factors. The former comprises among others the renin–angiotensin–aldosterone system (RAAS), arginine vasopressin (AVP), atrial natriuretic factor (ANF), and prostaglandins. The physical factors relate primarily to renal function and factors regulating osmotic pressure. Approximately 60% of body weight is water, which may be subdivided into intracellular volume (ICV) (40%) in which potassium and phosphate are the predominant cation and anion, respectively, and extracellular volume (ECV) (20%) dominated by sodium and chloride. ECV may further be subdivided into interstitial volume(15%) and plasma volume (PV) (5%) [1]. In principle ECV constitutes the internal environment, which is responsible for the transport of ions, nutrients and hormones vital to the cells. This term was introduced by the French physiologist, Claude Bernard, in 1885. The osmotic concentrations of ECV and ICV are equal under steady-state conditions, but any change result in an osmotic gradient and an immediate flux of water along this gradient until equilibrium is restored [2]. Hence a considerable passage of water occurs across the cell membrane, exemplified by the fact that the water content of an erythrocyte is exchanged 100 times per second without any netmovement of water [3]. Water passes mainly the cell membrane through protein channels, which in turn are influenced by osmotic differences generated by facilitated diffusion and active transport across the cell membrane. A normal subject ingests 2100ml water daily and synthesizes additionally 200ml by oxidation. Daily fluid output in a normal subject includes 700ml from the skin and lungs, 200ml from faeces, and sweat and a urinary output of 1400ml [4]. Between 5 and 10% of total body water is exchanged daily in healthy adults [1]. Total body water (TBW) is traditionally estimated by isotopic dilution. ECV and PV may also be estimated using this principle, whereas ICV assessment is calculated indirectly by combining measurements of TBW and ECV. The role of GH in this complex system is not fully established, but several reports suggest that it is important in body fluid regulation. More than 70 years ago anterior pituitary extracts were shown to induce fluid retention in rats [5] and two decades later GH-induced sodium and fluid retention was also demonstrated in man [6–8]. The sodiumand water-retaining effects of GH have subsequently been confirmed in several studies in normal man, in acromegalic patients and in GH-deficient patients [9–15]. Despite methodological heterogeneity most authors seem to agree that body fluid volume is decreased in GH-deficient adults and that GH treatment normalizes body fluid volume in these patients. There is also agreement that GH causes volume expansion, when administered in pharmacological doses to normal subjects and when secreted in excess in active acromegaly. Regarding the underlying mechanisms attention has focused on direct cellular action of GH [14] and a possible GH-induced stimulation of the renin–angiotensin– aldosterone system (RAAS) [8]. More recently other hormonal systems such as ANF [15], the prostaglandins [16], IGF-I [17], and nitric oxide [18] have been suggested to be involved. At present the sodium and fluidretaining effect of GH seems indisputable, whereas the underlying mechanisms appear to be diverse. www.elsevier.com/locate/ghir Growth Hormone & IGF Research 13 (2003) 55–74

Acute intracerebroventricular insulin microinjection after nitric oxide synthase inhibition of renal sodium handling in rats

The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Recent and growing evidence suggests that insulin or a nonapeptide-derived from the C-terminus of the insulin β-chain may influence many brain functions. However, there is little information on the insulin-activated neural pathways regulating urinary sodium excretion. Also, we examined the influence of nitric oxide synthase activity by chronic oral administration of N ω-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, after previous i.c.v. administration of insulin to unanesthetized, unrestrained rats that were randomly assigned to one of seven separated groups: (a) i.c.v. 0.15 M NaCl-injected (n = 11) and i.c.v. 126 ng (n = 11) insulin-injected rats; (b) i.c.v. insulin-injected in systemic L-NAME-treated (n = 10) and vehicle-treated insulin-injected rats (n = 10); and (c) subcutaneously (SC) insulin-injected rats (n = 5). We showed that centrally administered insulin produced increase in the urinary output of sodium (from 0.15 M NaCl: 855.6 ± 85.1 Δ%.min −1 to 126 ng insulin: 2055 ± 310.6 Δ%.min −1) and potassium (126 ng: from 0.15 M NaCl: 460.4 ± 100 Δ%.min −1 to 126 ng insulin: 669 ± 60.8 Δ%.min −1). The urinary sodium excretion response to i.c.v. 126 ng insulin microinjection was significantly abolished by previous systemic treatment of animals with 15 mg/kg/day L-NAME (from vehicle + 126 ng insulin: 1935 ± 258.3 Δ%. min −1 to L-NAME + 126 ng insulin: 582.3 ± 69.6 Δ%. min −1). In addition, we showed that insulin-induced natriuresis occurred by increasing post-proximal tubule sodium rejection (FEPP Na), despite an unchanged glomerular filtration rate (C Cr). The current data suggests the novel concept that CNS NO-dependent neural pathways may play an instrumental role on efferent insulin-sensitive nerve activity from periventricular region. Speculatively, it seems interesting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature, and that defects in this efferent signal could result in insulin central resistance, inability of renal tubules to handle the hydro electrolyte balance and hypertension.

Dehydration in stressed ruminants may be the result of a cortisol-induced diuresis.

The effect on water and electrolyte balance of stress, simulated by intravenous infusion of cortisol, was studied using 24 18-mo-old Merino wethers (37.0 +/- 0.94 kg mean body weight [BW]) over 72 h. The sheep were allocated to one of four groups: 1) no water/no cortisol (n = 6); 2) water/no cortisol (n = 4); 3) no water/cortisol (n = 6); and 4) water/cortisol (n = 4). Animals allocated to the two cortisol groups were given 0.1 mg x kg BW(-1) x h(-1) of hydrocortisone suspended in isotonic saline to simulate stress for the duration of the experiment. Total body water, plasma cortisol, osmolality and electrolytes, and urine electrolytes were determined at 24-h intervals for 72 h. In the presence of cortisol, total body water was maintained in the face of a water deprivation insult for 72 h. Water deprivation alone did not induce elevated plasma concentrations of cortisol, in spite of a 13% loss of total body water between 48 and 72 h. Infusion of cortisol was found to increase urine output (P = 0.003) and decrease total urinary sodium output (P = 0.032), but had no effect on plasma electrolyte levels or water intake. Water deprivation was found to increase plasma sodium concentrations (P = 0.037). These results indicate that sheep given cortisol to simulate stress suffer from a loss of body water in excess of that associated with a loss of electrolytes, and support the hypothesis that elevated physiological concentrations of cortisol induce a diuresis in ruminants that contributes to dehydration.

Hypoxic ventilatory response, ventilation, gas exchange, and fluid balance in acute mountain sickness.

To examine whether sea-level hypoxic ventilatory responses (HVR) predict acute mountain sickness (AMS) and document temporal changes in ventilation, HVR, gas exchange, and fluid balance, we measured these parameters at low altitude (100 m) and daily during 3 days at high altitude (4559 m). At low altitude, there were no significant differences in rest or exercise isocapnic HVR, poikilocapnic HVR at rest, and hypercapnic ventilatory response between 12 subjects without significant AMS and 11 subjects who fell sick. No low altitude ventilatory responses correlated with AMS or fluid balance at high altitude. On day 1, isocapnic HVR was significantly lower in the AMS group [0.86 +/- 0.43 (SD) vs. 1.43 +/- 0.63 L/min/% Sa(O2), p < 0.05). AMS was associated with higher AaD(O2), lower Pa(O2), and Sa(O2), while Pa(CO2) was not different between subjects with and without AMS. Both groups showed equivalent reductions in urine volume, sodium output, and gain in body weight on day 1 while climbing to 4559 m, but on day 2 only subjects without AMS had diuresis, natriuresis, and weight loss. We conclude that (1) susceptibility to AMS, fluid balance, and ventilation at high altitude cannot be predicted by low altitude HVR testing and (2) that the failure to increase HVR on arrival at high altitude and impaired gas exchange, possibly due to interstitial edema, may account for the more severe hypoxemia in AMS.

Autonomic control of protein production by the parotid gland of the sheep

The role of adrenoceptors in the control of parotid salivary function has been investigated in anaesthetized sheep. The enhancement of parotid protein output that occurs when the parasympathetic and sympathetic innervations to the gland are stimulated simultaneously in bursts at a low frequency (20 Hz for 1 s at 10-s intervals) was effectively abolished by pretreatment with propranolol (≥1.0 mg kg −1, i.v., P<0.001), without a comparable reduction in the flow of saliva or in the output of sodium or potassium. Secretion of protein was similarly augmented by simultaneous stimulation of the sympathetic innervation and an intracarotid infusion of acetylcholine (0.4–0.6 μg min −1 g gland −1). This effect was also abolished by pretreatment with propranolol. Pretreatment with phentolamine (>1.0 mg kg −1, i.v .) had no effect on the output of protein that occurred during combined stimulation of the parasympathetic and sympathetic innervations but increased the flow of saliva and the output of electrolytes. Stimulation of the parasympathetic innervation to the parotid gland caused a substantial fall in vascular resistance, which was reduced by the administration of atropine (0.5 mg kg −1). Stimulation of the sympathetic innervation caused a substantial rise in parotid vascular resistance in atropinized sheep. This effect was greater during continuous stimulation than during intermittent stimulation and enhanced by pretreatment with propranolol. It was virtually eliminated by pretreatment with phentolamine. It is concluded that the enhancement of protein output from the ovine parotid gland, that occurs during combined stimulation of the parasympathetic and sympathetic innervations at relatively low frequencies, depends upon interaction between cholinergic muscarinic and β-adrenergic receptors. The vasoconstriction that occurs during sympathetic stimulation alone can be accounted for by activation of α-adrenoceptors.