Copyright (c) 2010 All rights reserved. http://works.bepress.com/sopava Recent documents in Susan C. Opava-Stitzer en-us Wed, 21 Jul 2010 15:18:07 PDT 3600 http://works.bepress.com/sopava/12 http://works.bepress.com/sopava/12 Wed, 07 May 2008 12:54:40 PDT A state of chronic dehydration with reduced plasma volume, decreased blood pressure, and increased plasma renin activity (PRA) has been demonstrated in rats with hereditary hypothalamic diabetes insipidus (DI) rats. In this situation decreased renal perfusion and glomerular filtration rate might result in sodium retention. On the other hand, the DI rat also suffers from mineralocorticoid deficiency which might result in salt wasting. In addition it has recently been shown that in contrast to normal rats, there are no differences between superficial cortical and juxtamedullary nephrons of the DI rat with respect to single nephron filtration rate, glomerular volume, and proximal tubular length. This lack of internephron heterogeneity might also affect renal sodium handling in the DI rat. It thus seems of particular interest to evaluate the natriuretic response of DI rats to volume expansion. In the present study, the natriuetic responses of DI and normal Long-Evans rats to acute and chronic volume expansion were compared. Other factors involved in sodium handling, namely mineralocortoids and renal (Na+ + K+) - ATPase activity, were also studied. Susan C. Opava-Stitzer Research Publications http://works.bepress.com/sopava/11 http://works.bepress.com/sopava/11 Wed, 07 May 2008 12:54:37 PDT Since its discovery in 1961, it has become apparent that the Brattleboro (DI) rat is a useful model for the study of a variety of physiological problems in addition to the obvious one of the role of antidiuretic hormone (vasopressin, ADH) in urine concentration and water balance. In the study of the control of extracellular fluid volume and electrolyte balance, in particular, the DI rat offers a unique opportunity to observe the spontaneous interaction of homeostatic mechanisms when a single disturbance, namely the absence of ADH, has been introduced. This review will attempt to present a comprehensive description of the state of sodium and potassium balance in the DI rat. Although some data exist on the handling of other electrolytes these have not been studied extensively. Mention will also be made of the multiple factors that may influence electrolyte balance in the Brattleboro rat. New data, obtained by Opava-Stitzer and Fernandez-Repollet, will be included when relevant. Susan C. Opava-Stitzer Research Publications http://works.bepress.com/sopava/14 http://works.bepress.com/sopava/14 Wed, 07 May 2008 12:54:17 PDT Rats with hereditary hypothalamic diabetes insipidus (so-called DI rats) have elevated plasma renin levels. Although the mechanism responsible for this condition has not be elucidated, it seems reasonable to postulate that the absence of ADH and/or the hypokalemia previously reported in these rats might contribute to the elevation of plasma renin concentration (PRC). Evidence in favor of this hypothesis emerges from studies in which both ADH and potassium have been shown to inhibit renin release. In an attempt to examine the relative roles of ADH and potassium in the regulation of renin secretion, PRC was measured in DI rats maintained on a potassium-free, normal potassium, or high potassium diet in the presence and absence of ADH treatment. Emma Fernandez-Repollet Research Publications http://works.bepress.com/sopava/13 http://works.bepress.com/sopava/13 Wed, 07 May 2008 12:53:44 PDT Antidiuretic horomone (ADH) is known to inhibit renin secretion in many species, but the mechanism of this inhibition and its importance in the control of renin secretion are unknown. Susan C. Opava-Stitzer Research Publications http://works.bepress.com/sopava/8 http://works.bepress.com/sopava/8 Tue, 22 Apr 2008 17:01:47 PDT Arterial plasma renin activity (PRA) was measured using radioimmunoassay techniques in pentobarbital-anesthetized dogs. Acute saline loading (40-60ml 150mm NaCl/kg body weight, or 20ml 300mm NaCl/kg body weight, i.v.) reduced PRA from control level in 7 dogs. Despite continued increases in filtered and excreted masses of Na, subsequent partial aortic clamping increased PRA in proportion to the degree of reduction in renal perfusion pressure. In 6 other dogs aortic clamping super-imposed on total ureteral occlusion led to changes in PRA which were inversely associated with renal perfusion pressure. These results suggest a controlling mechanism for renin secretion sensitive to some hemodynamic parameter. Paul C. Churchill Research Publications http://works.bepress.com/sopava/10 http://works.bepress.com/sopava/10 Tue, 22 Apr 2008 17:01:38 PDT To examine the contribution of papillary structures to the overall process of urine dilution and concentration at high rates of flow, studies were performed in unilaterally papillectomized kidneys (PX). Comparison of kidney weights in sham-operated and PX rats revealed a significant reduction in total weight of the latter. Papillary length removed was 3045 ± 423 μm. GFR was reduced by 24% and 45% in sham and PX kidneys when compared to their contralateral controls. Under hydropenic conditions, maximal urine concentrating ability (Umax) was comparable in control and sham kidneys but was 59% less in PX kidneys. Fractional sodium excretion during hydropenic conditions was comparable in control and PX kidneys. Nonurea solute [(Na + K) x 2] concentration in the medulla of control and papillectomized kidneys was essentially the same. Free water reabsorption (TcH2O) as a function of osmolar clearance (C0sm) was comparable in control, sham, and PX kidneys. At C0sm greater than 25%, there was a tendency for TcH2O to fall in both control and PX kidneys. Free water clearance (CH2O) during hypotonic saline diuresis rose in almost linear fashion as a function of urine flow (V) without clear-cut differences between control and PX kidneys. There was, however, a tendency for CH2O to be slightly higher at any level of V in PX than in control kidneys. These experiments suggest that nephrons with long loops reaching into the papilla and the terminal collecting ducts are not essential for the maximal generation and reabsorption of free water. Manuel Martinez-Maldonaldo Research Publications http://works.bepress.com/sopava/9 http://works.bepress.com/sopava/9 Tue, 22 Apr 2008 17:01:10 PDT 1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition. Emma Fernandez-Repollet Research Publications http://works.bepress.com/sopava/6 http://works.bepress.com/sopava/6 Mon, 21 Apr 2008 16:09:22 PDT 1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats).2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats.3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats.4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets.5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive.6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance.7. ADH and potassium may inhibit renin secretion via different mechanisms of action. Emma Fernandez-Repollet Research Publications http://works.bepress.com/sopava/5 http://works.bepress.com/sopava/5 Mon, 21 Apr 2008 16:09:18 PDT 1. Free water clearances were measured during infusion of hypotonic saline, glucose, urea, and mannitol in Brattleboro rats. For each solute the free water clearances were plotted using either V or (CH2O + CNa) as the distal tubular delivery term. 2. In all cases the use of (CH2O + CNa) as distal delivery term yielded a steeper relationship than when V was used. There were no significant differences in the CH2O to V relationship when saline, glucose and mannitol was the solute infused. Urea, however, resulted in a curve with a slope significantly less than that for the other solutes. 3. When CH2O was plotted against (CH2O + CNa) there was still no significant difference between the slopes of the curves during saline or mannitol infusion. Use of this delivery term, however, resulted in a slope during glucose infusion which was significantly greater than that during saline or mannitol infusion. The slope for urea infusion remained lower than that for any other solute. 4. Regardless of the delivery term used, there was no significant difference in the slopes of the curves for awake Wistar and awake Brattleboro rats during mannitol infusion. This indicates that the awake rat is a suitable model for free water clearance studies. 5. The results indicate that NaCl and mannitol are both adequate for free water clearance and that (CH2O + CNa) is a better index of distal delivery than V. Manuel Martinez-Maldonaldo Research Publications http://works.bepress.com/sopava/4 http://works.bepress.com/sopava/4 Mon, 21 Apr 2008 16:09:15 PDT A defect in the ability to concentrate or dilute the urine can be easily recognized by the maximum or minimum urine concentration the patient is able to achieve. Maximum concentrating ability (Umax) is determined by the urine osmolality reached after a fixed period of dehydration and maximal diluting ability (Umin) by the minimum osmolality of the urine after the oral ingestion of a fixed water-load. These indices, however, do not allow an understanding of the pathophysiological alterations leading to the presence of the defect. Manuel Martinez-Maldonaldo Contributions to Books http://works.bepress.com/sopava/3 http://works.bepress.com/sopava/3 Mon, 21 Apr 2008 16:09:12 PDT Although several studies have indicated that antidiuretic hormone (ADH) enhances the phagocytic function of the reticuloendothelial system (RES) in shock syndromes, it remains unknown what influence ADH exerts upon the individual phagocytic components of this system. The present investigation was designed to evaluate the effects of endogenous ADH on the phagocytic activity of peritoneal macrophage cells. As a phagocytic stimuli, fluorescent methacrylate microbeads were injected intraperitoneally into Brattleboro (ADH deficient) and normal Long Evans rats in the presence and absence of exogenous ADH. Peritoneal cells were harvested 19-22 hr after the administration of the microbeads and the percent phagocytosis was determined in macrophage cells using a fluorescence-activated cell sorter (FACS II). Our results indicate that the percentage of peritoneal macrophages ingesting the fluorescent methacrylate microbeads was significantly reduced in the absence of ADH (Brattleboro rats: 5.4 ± 0.6% versus Long Evans rats: 16.8 ± 2.3%; p < 0.001). In addition, our data demonstrate that exogenous administration of ADH significantly enhanced macrophage phagocytosis in Brattleboro (14.7 ± 2.2%) and normal Long Evans (49.6 ± 4.5%) rats. These data suggest, for the first time, that endogenous ADH might play a modulatory role in the phagocytic activity of a specific component of the RES, namely, the macrophage cell. Emma Fernandez-Repollet Research Publications http://works.bepress.com/sopava/7 http://works.bepress.com/sopava/7 Mon, 21 Apr 2008 16:08:53 PDT The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (μmole P04/mg protein/ hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 ± 2.0, 37 ± 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 ± 0.9) and plasma aldosterone (20.0 ± 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 ± 9 weanling SHR, 89 ± 7 weanling WKY, 73 ± 11 adult SHR, 84 ± 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR. Jose L. Cangiano Research Publications http://works.bepress.com/sopava/2 http://works.bepress.com/sopava/2 Wed, 16 Apr 2008 16:57:24 PDT Distal nephron function of the rat during lithium chloride infusion. Chronic lithium (Li) administration in the rat leads to reduced renal concentration (TCH2O) without alterations in renal dilution (CH2O). To examine the acute effects of lithium on TCH2O and CH2O, rats were infused with a solution composed of 1% sodium chloride and 1% lithium chloride or a 0.225% lithium chloride solution at rates from 0.06 to 0.5 ml/min. In six rats, infusion of the sodium-lithium solution resulted in marked inhibition of TCH2O at any level of osmolar clearance (C0sm) when compared to animals receiving 2.2% sodium chloride alone. Administration of amiloride, 40 or 80μg/kg BW/min throughout the experiment, to ten rats infused with the sodium-lithium solution, resulted in marked improvement of TCH2O to C0sm relationship. Infusion of 0.255% lithium chloride to nine rats undergoing water diuresis led to marked reductions in CH2O as a function of distal delivery (V) when compared to rats receiving 0.225% sodium chloride alone. Infusion of amiloride did not improve the CH2O to V relationship in ten rats undergoing hypotonic lithium chloride infusion. These studies suggest that lithium interferes with sodium chloride reabsorption in the distal nephron, particularly the loop of Henle, and also reduces the permeability of the collecting duct to water. Amiloride, probably by interfering with lithium transport into collecting duct cells, corrects partially the TCH2O defect by preventing water permeability changes. The lack of effect of amiloride in CH2O studies may relate to the fact that collecting duct permeability is already at its lowest. The studies suggest that lithium ions retard chloride reabsorption in the ascending limb as inferred from the CH2O and TCH2O studies. Both chloride and sodium ions appear to be required for normal loop function. Manuel Martinez-Maldonaldo Research Publications