Water extraction from the inner medullary collecting tubule system: a role for urea

A case study was reported in which a 9-year-old male autistic boy was initially trained to discriminate between two auditory stimuli and two visual stimuli. He was then tested for overselective responding to bidimensional combinations of the four stimuli. It was hypothesized that the overselectivity results reported in previous studies were partially a function of a procedure in which autistic children were reinforced for responding in the presence of a multidimensional stimulus complex and then tested with individual stimuli. The child in the present investigation, with the alternative procedure, did not demonstrate overselective responding. Two interpretations of the results were presented, neither of which was consistent with an overselectivity theory. Future research should delineate the specific conditions which produce overselective responding, and suggest methods to facilitate more adaptive responding of autistic children.     

Transformation of rat inner medullary fibroblasts to myofibroblasts in vitro

Renal fibroblasts play a major role in the pathogenesis of renal interstitial fibrosis. This process is associated at least in some forms of interstitial fibrosis with a differentiation of fibroblasts into myofibroblasts, characterized by the de novo expression of alpha-smooth muscle (alpha-sm) actin and/or desmin. Both the mechanisms underlying this differentiation and their effects on cellular function are poorly understood. In vitro studies are difficult since the phenotypes of fibroblasts in culture have as yet not been well defined. We have, therefore, examined the phenotype of inner medullary fibroblasts (IMF) during the transition from in vivo to in vitro in various cell fractions derived from the inner medulla of healthy rats. IMF were positive for the lectin BSL-1 and negative for markers of endothelial cells. IMF first lost their prominent lipid droplets in vitro. Subsequently they developed cytoplasmic processes accompanied by a decrease in their reactivity for the lectin BSL-1 from strong to weak. From day 3 in primary culture, exclusively these weakly positive BSL-1 cells showed a de novo expression of alpha-sm actin (day 4 of primary culture, 75 +/- 4%; day 20, 94 +/- 2%) and desmin (day 4, 43 +/- 8%; day 20, 66 +/- 6%), classifying them as myofibroblasts. This transformation depended on culture conditions. In a mixed coculture with inner medullary collecting duct (IMCD) cells the transformation of IMF was largely absent: a significantly greater number of strong BSL-1 positive cells contained prominent lipid droplets (39 +/- 4 vs. 19 +/- 4%, P < 0.05) on day 4 of primary culture, and the transition of strongly to weakly positive BSL-1 IMF was almost completely blocked. By reducing the seeding density of IMCD cells the effect of this condition on IMF transformation could be largely abolished. This first detailed phenotypic characterization of rat fibroblasts during the transition from in vivo to in vitro demonstrates that these cells-depending on culture conditions-differentiate to myofibroblasts within a few days of primary culture and that subcultured IMF exhibit predominantly this phenotype. The presented model may serve as a useful tool for the in vitro study of myofibroblast formation and the consequences of such a differentiation for the physiological functions of IMF.     

Novel 13A antigen is an integral protein of the basolateral membrane of rat glomerular podocytes

BACKGROUND: We described recently the 13A monoclonal antibody recognizing a 120 kilodalton protein located at the bases of podocyte foot processes in rat glomeruli. The antigen was extracellular, either a component of the glomerular basement membrane or an integral membrane protein. As only few markers exist for the basal domain of the podocyte membranes, we wanted to characterize the antigen further. EXPERIMENTAL DESIGN: The distribution of the 13A antigen in rat tissues and cultured cells was studied by immunofluorescence and immunoelectron microscopy. Cultured cells were also used for its biochemical and functional characterization. RESULTS: The antigen was detected in several rat epithelial and smooth muscle tissues. In polarized epithelia, it was restricted to the basolateral membranes, and in stratified epithelia, to the basal cell layer. In contrast to its limited distribution in vivo, the antigen was detected in vitro in several cultured fibroblastoid or epithelial rat cell lines, and in cultured mesangial cells. In nonpolarized cells, it had a diffuse granular distribution at the cell surface, and at the ventral surface, it colocalized with vinculin in areas resembling focal adhesions, as shown by double immunofluorescence staining. In polarized epithelial cells, the 13A antigen was concentrated at the basolateral membranes. By immunoelectron microscopy, it was often present at the tips of cell extensions and at adhesion sites. Pretreatment of cryostat sections or cultured cells with trypsin partially inhibited antibody binding, whereas detergents abolished it totally. The antigen of cultured cells could not be identified by Western blotting or immunoprecipitation techniques. The antibodies did not seem to affect cell growth or adhesion. CONCLUSIONS: The 13A antigen is an integral membrane protein of several rat epithelial tissues and cultured cells, and is particularly abundant in the podocyte foot processes. Although its identity and function remain unknown, the 13A protein is a valuable marker for the basal membrane domain of the podocyte.     

Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver

A modified "Samson" sucrose fading procedure was used to establish voluntary consumption of a 20% ethanol (EtOH) solution in male Sprague-Dawley rats for 18 consecutive months. Intakes were stable over the life span, and corresponded to the moderate to high levels of intake typically observed in human "social" drinkers and alcoholics. The Morris Water Maze (WM), Olton Radial Arm Maze (RM), and a "balance beam" test were used to assess the effects of alcohol and aging on spatial memory and motor function. Aged EtOH-consuming rats (AGED/ALC) demonstrated impaired task acquisition, relative to aged controls (AGED), not reaching criterion performance in either spatial memory task even when given four additional days of training. AGED/ALC rats scored significantly lower on percent correct out of the first eight arm entries, and committed more perseverative errors in the RM. There were no significant performance differences between AGED and AGED/ALC rats on a balance beam test of fine motor coordination and equilibrium, suggesting that deficits observed in the RM and WM were not related to differential motor functioning. These results demonstrated that long-term, moderate, oral self-administration of EtOH, within the range typically consumed by humans, had adverse effects on spatial memory in rats, and that such a pattern of EtOH consumption seemed to exacerbate the decline in cognitive functioning associated with normal aging.     

Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats

Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg x H2O to 925 +/- 103 mosmol/kg x H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia.     

Hepatic uptake of choline in rat liver basolateral and canalicular membrane vesicle preparations

Choline, an endogenous quaternary ammonium ion, is transported into the liver by both saturable and nonsaturable processes. The objective of the present investigation was to determine the driving force(s) for uptake of choline in rat liver basolateral membrane (blLPM) and canalicular membrane (cLPM) vesicles. Choline is transported into an osmotically sensitive intravesicular space in both blLPM and cLPM. Uptake of [3H]choline into both blLPM and cLPM exhibited temperature dependence (0 degree C vs. 37 degrees C). A valinomycin-induced inside-negative K+ diffusion potential significantly stimulated initial uptake of [3H]choline in both vesicles. Choline uptake in blLPM and cLPM was not stimulated in the presence of an inwardly directed sodium gradient or an outwardly directed H+ gradient, and ATP did not enhance choline uptake in cLPM. Choline itself and structurally similar derivatives, such as hemicholinium-3 and succinylcholine, inhibited [3H]choline uptake 11 to 92% (at 10-fold higher concentrations) in blLPM and cLPM. Other cations, including N1-methylnicotinamide, thiamine and d-tubocurarine, and cardioglycosides did not inhibit choline transport in either vesicle preparation. In addition, [3H]choline uptake into both blLPM and cLPM was enhanced when vesicles were preloaded with nonradiolabeled choline (trans-stimulation). Kinetic studies indicated that choline was transported into blLPM by both saturable and passive processes and into cLPM predominantly by a saturable process. These results suggest that the transport of choline is likely mediated by a potential-sensitive conductive pathway in both blLPM and cLPM. The electrogenic pathway in cLPM may play a role in the reabsorption of choline from bile.     

Activity of the basolateral K+ channels is coupled to the Na+-K+-ATPase in the cortical collecting duct

Microelectrode and patch-clamp techniques were used in the isolated cortical collecting duct to study the effects of stimulating Na+-K+-ATPase by raising bath K+ (Fujii Y and Katz AI. Am J Physiol Renal Fluid Electrolyte Physiol 257: F595-F601, 1989 and Muto S, Asano Y, Seldin D, and Giebisch. Am J Physiol Renal Physiol 276: F143-F158, 1999) on the transepithelial (VT) and basolateral membrane (VB) voltages and basolateral K+ channel activity. Increasing bath K+ from 2.5 to 8.5 mM resulted in an initial hyperpolarization of both VT and VB followed by a delayed depolarization. The effects of raising bath K+ on VT and VB were attenuated by decreasing luminal Na+ from 146.8 to 14.0 mM and were abolished by removal of luminal Na+, whereas those were magnified in desoxycorticosterone acetate (DOCA)-treated rabbits. Increasing bath K+ also led to a significant reduction of the intracellular Na+ and Ca2+ concentrations. The transepithelial conductance (GT) or fractional apical membrane resistance (fRA) were unaltered during the initial hyperpolarization phase, whereas, in the late depolarization phase, there were an increase in GT and a decrease in fRA, both of which were attenuated in the presence of low luminal Na+ (14.0 mM). In tubules from DOCA-treated animals, bath Ba2+ not only caused a significantly larger initial hyperpolarization of VT and VB but also blunted the late depolarization by high bath K+. Nomega-nitro-l-arginine methyl ester (l-NAME) partially mimicked the effect of Ba2+ and decreased the amplitude of the late depolarization. Patch-clamp experiments showed that raising bath K+ from 2.5 to 8.5 mM resulted in an increased activity of the basolateral K+ channel, which was absent in the presence of l-NAME. We conclude that stimulation of Na+-K+-ATPase increases the basolateral K+ conductance and that this effect involves suppression of nitric oxide-dependent inhibition of K+ channels.     

Characterization of prostaglandin production in tissue culture of rat renal medullary cells

The purpose of our studies was to examine the role of the nervous system in arrhythmias produced by digitalis overdose and coronary artery occlusion in the cat. This was done by observing the effect of these arrhythmogenic procedures on cardiac efferent neural activity and then determining whether any observed alteration in neural activity contributed to the cardiac rhythm disturbances evoked by digitalis and coronary artery occlusion. Our data indicate that both procedures used to evoke arrhythmias activate each division of the autonomic nervous system. Activation of the sympathetic nervous system resulted in a deleterious effect on cardiac rhythm whereas activation of the parasympathetic nervous system, in general, resulted in a beneficial effect on cardiac rhythm. With coronary occlusion, the role exerted by the nervous system depended on the anatomic location of the involved myocardium. Studies directed at elucidating the mechanisms whereby the nervous system caused cardiac rhythm disturbances indicated that there may be an important difference between the antiarrhythmic efficacy of beta-adrenergic blockade and bilateral stellate ganglionectomy. The latter procedure proved to be a more effective way of removing deleterious sympathetic neural effects on the heart. In conclusion, our findings suggest that the development of new drugs for treating arrhythmias resulting from digitalis and coronary occlusion should be aimed at finding drugs that act to either depress central sympathetic outflow or enhance parasympathetic effects on the ventricle.     

Localization of inducible nitric oxide synthase in acute renal allograft rejection in the rat

There is increasing evidence for a role for nitric oxide (NO) in the alloimmune response and induction of NO synthesis occurs during allograft rejection. The aim of this study was to investigate the source of NO synthesis in rejecting allografts. Localization of inducible nitric oxide synthase (iNOS) was studied by immunohistochemistry, in a rat model of acute renal allograft rejection, in unmodified Lewis recipients in which rejection is complete 7 days after transplantation of F1 hybrid Lewis-Brown Norway kidneys. High levels of iNOS expression were found in infiltrating mononuclear cells in glomeruli and interstitium of rejecting kidneys; there was no expression in parenchymal renal cells, or in control isografts of either rat strain. Expression of iNOS in the cortex was present from 4 to 6 days posttransplantation, and had declined by the 7th day, where expression was principally in the medulla. The pattern of iNOS staining was similar to ED1 staining, a marker for rat macrophages. These findings suggest that infiltrating macrophages in the graft reaction are a prominent source of NO; this iNOS expression supports a role for NO in the modulation of local allogeneic responses, and possibly as a mediator of cytotoxic graft damage.     

Loop diuretics act directly on adenylate cyclase in rat renal tubular basolateral membranes

We have reported previously that loop diuretics, especially azosemide and ethacrynic acid, may act not only on the AVP receptor site, but also on the post-AVP receptor site in rat renal tubular basolateral membranes. The purpose of this study was to examine whether loop diuretics (furosemide, azosemide, ethacrynic acid) affect the post-AVP receptor components, using GTP-gamma S, forskolin and cholera toxin as tools acting distal to the receptor. Adenylate cyclase activity stimulated by 10(-9)M AVP was inhibited more potently by azosemide and ethacrynic acid than by furosemide at the concentration of 10(-3) M. Azosemide and ethacrynic acid at concentrations above 10(-4) M also significantly decreased the enzyme activity that was stimulated by 10(-7) M GTP-gamma S and 10(-5)M forskolin, while significant inhibition by furosemide was observed only at 10(-3)M. In addition, the inhibitory effect of these loop diuretics on cholera toxin-stimulated enzyme activity was almost similar to the results observed in AVP-, GTP-gamma S- or forskolin-stimulated the enzyme activity. From these results, we conclude that loop diuretics, especially azosemide and ethacrynic acid, directly affect adenylate cyclase in part as well as the AVP receptor site.     

Inhibition of myo-inositol transport causes acute renal failure with selective medullary injury in the rat

Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure. Under aerobic conditions, NO is transformed into its higher oxides (N2O4, NO2, NO/NO2 or N2O3) and oxoperoxonitrate (currently named peroxynitrite) by coupling with superoxide. Previous studies have shown that these reactive nitrogen species should be involved in vivo in the transformation of cysteine and tyrosine into the corresponding nitrosothiol and 3-nitrotyrosine. In the present study, attention has been focused on the relative reactivities of HNO2, peroxynitrite, and NO in the presence of dioxygen, towards the arginine and tyrosine residues of the peptide angiotensin II. Nitration of the tyrosine residue is clearly the main reaction with peroxynitrite. By contrast, besides 20% of nitration of the tyrosine residue, NO in the presence of dioxygen leads to nitrosation reactions with the arginine residue similar to those observed with HNO2 at pH 5, possibly through the intermediate N2O3 reactive species. Angiotensin II is converted for the most part to peptides having lost either a terminal amine function or the whole guanido group, leading respectively to citrulline-containing angiotensin II or to a diene derivative. Identification established mainly by tandem mass spectrometry of peptidic by-products allows us to propose a cascade of nitrosations of all the amine functions of the arginine residue. Further in vivo studies show that transformations of the arginine residue in angiotensin II do not alter its vasoconstrictive properties, whereas nitration of the tyrosine residue totally inhibits them.     

Regulation and possible physiological role of the Ca(2+)-dependent K+ channel of cortical collecting ducts of the rat

In the luminal membrane of rat cortical collecting duct (CCD) a big Ca(2+)-dependent and a small Ca(2+)-independent K+ channel have been described. Whereas the latter most likely is responsible for the K+ secretion in this nephron segment, the function of the large-conductance K+ channel is unknown. The regulation of this channel and its possible physiological role were examined with the conventional cell-free and the cell-attached nystatin patch-clamp techniques. Patch-clamp recordings were obtained from the luminal membrane of isolated perfused CCD segments and from freshly isolated CCD cells. Intracellular calcium was measured using the calcium-sensitive dye fura-2. The large-conductance K+ channel was strongly voltage- and calcium-dependent. At 3 mumol/l cytosolic Ca2+ activity it was half-maximally activated. At 1 mmol/l it was neither regulated by cytosolic pH nor by ATP. At 1 mumol/l Ca2+ activity the open probability (Po) of this channel was pH-dependent. At pH 7.0 Po was decreased to 4 +/- 2% (n = 9) and at pH 8.5 it was increased to 425 +/- 52% (n = 9) of the control. At this low Ca2+ activity the Po of the channel was reduced by 1 mmol/l ATP to 8 +/- 4% (n = 6). Cell swelling activated the large-conductance K+ channel (n = 14) and hyperpolarized the membrane potential of the cells by 9 +/- 1 mV (n = 23). Intracellular Ca2+ activity increased after hypotonic stress. This increase depended on the extracellular Ca2+ activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiration and ion permeability of the inner membrane in rat "sodium" liver mitochondria

Ion permeability of internal membrane and a respiration in isolated rat liver mitochondria, further related to as "sodium ones", were studied following replacement of K+ ions for Na+ ones in the mitochondrial matrix. As compared with the control ("potassium mitochondria"), state 4 respiration in the sodium mitochondria, energized by succinate, was shown to be enhanced in KCl or sucrose media. Oxygen consumption rates in the sodium mitochondria, being in state 3 or stimulated by 2,4-dinitrophenol, were lower than rates for the control mitochondria. This effect was much pronounced in the sucrose medium. The coefficients, characterizing the distribution of 137Cs between mitochondria and the medium, were lower for the sodium mitochondria than for the control in the presence of 2.5 mM succinate and 10(-8) M valinomycin. In comparison with the control, a more extensive swelling for the sodium mitochondria was found, first, in the medium containing 25 mM K-acetate and 100 mM sucrose for succinate-energized mitochondria, and second, in the medium containing 125 mM NH4NO3 without mitochondrial energization. Changes disclosed in respiration, swelling and coefficients of 137Cs distribution for the sodium mitochondria are supposed to be caused by non-uniform effects of Na+ and K+ ions on the water structure of mitochondrial matrix, ion permeability of internal membrane, and the activity in oxidative phosphorylation enzymes.     

Effects of urinary ouabain-like factors and vanadium diascorbate on calcium mobilization in porcine inner medullary collecting duct cells: comparison with the effects of ouabain and vasopressin

It is speculated that ouabain-like factors (OLF) play a role in the pathogenesis of volume-dependent hypertension. In previous studies we isolated a more polar OLF-1 and a more apolar OLF-2 from the urine of healthy subjects after 5 days on a high sodium intake (>400 mmol/day) by gel chromatography (Sephadex G-25 and G-10) and reverse-phase HPLC. We subsequently identified the chemical structure of OLF-2 as vanadium (V(IV)) diascorbate. OLF-1, OLF-2, and vanadium diascorbate inhibited dose-dependently porcine Na-K-ATPase in vitro. Because the inner medullary collecting duct (IMCD) plays a crucial role in the long-term regulation of body fluid volume, in the present study we investigated the effects of urinary OLF-1 and OLF-2, and of vanadium diascorbate in comparison to ouabain and vasopressin (AVP) on calcium mobilization, ie, on free calcium concentration [Ca2+]i, in cultured porcine IMCD cells. [Ca2+]i was determined by the fura-2 method in IMCD cells isolated by hypotonic treatment and density gradient centrifugation from fresh porcine kidneys. Assuming an approximate molecular weight (MW) of 400 for OLF-1 and OLF-2, OLF-1 (10(-4) mol/L) produced a slow increase in [Ca2+]i from 39 +/- 10 to 169 +/- 21 nmol/L (n = 7 ) after 4 min. Similarly, OLF-2 (10(-4) mol/L) resulted in an increase in [Ca2+]i from 74 +/- 20 to 216 +/- 52 nmol/L (n = 7) after 4 min. Vanadium diascorbate (MW 403) dose-dependently increased [Ca2+]i . At a concentration of 10(-6) mol/L it increased [Ca2+]i from 46 +/- 5 to 149 +/- 9 nmol/L (n = 5) after 4 min. A similar slow increase in [Ca2+]i was found with ouabain (10(-6) mol/L), which increased [Ca2+]i from 61 +/- 22 to 180 +/- 29 nmol/L (n = 5) after 4 min in contrast to AVP (10(-7) mol/L), which rapidly increased [Ca2+]i from 48 +/- 10 to 299 +/- 32 nmol/L (n = 4) within 30 sec. Thus, OLF-1, OLF-2, and Vanadium diascorbate, the active component of OLF-2, reveal similar effects as ouabain on IMCD cells, ie, they produce a slow increase in [Ca2+]i as expected from inhibition of Na-K-ATPase. The physiologic or pathologic roles of these and additional OLF in body fluid and blood pressure regulation and in hypertension have yet to be evaluated.     

Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.     

Magnesium transport across the basolateral plasma membrane of the fish enterocyte

The aim of the study was to assess the influence of aortic valve replacement on left ventricular size and muscle hypertrophy according to the type of preexisting valve disease (aortic stenosis, insufficiency or combined disease). The study group consisted of 143 consecutive patients (pts) after aortic valve replacement (109 men, 34 women, mean age 48.1 +/- 10.9 years). Reason for the operation was aortic stenosis in 35 pts, aortic insufficiency in 64 pts and combined disease in 44 pts. Echocardiography was performed before surgery, 1 month and 1 year after operation, and yearly during 5-year follow-up. Transvalvular aortic pressure gradients decreased significantly after valve replacement in all subsets without further changes during follow-up (Pmax (mmHg): from 54.2 +/- 20.7 to 17.9 +/- 9.6 in combined disease pts, from 72.3 +/- 19.9 to 21.6 +/- 14.6 in aortic stenosis and from 34.5 +/- 24.2 to 15.6 +/- 11.3 in aortic insufficiency pts, respectively, P < 0.0005). One year after surgery the diastolic dimension of the left ventricle decreased significantly in all subjects, whereas the systolic dimension only in aortic insufficiency and combined disease pts (from 44 +/- 11.8 to 31.6 +/- 5.4 mm, P < 0.001 and from 41.9 +/- 11.5 to 33 +/- 6.7 mm, P < 0.05, respectively). Further decrease of both diastolic and systolic dimensions was observed only in the aortic insufficiency group. Ejection fraction of left ventricle increased only in combined disease pts (from 51.6 +/- 10% to 56.8 +/- 8.2%, P < 0.05). Wall thickness of the left ventricle decreased 1 year after valve replacement only in the aortic stenosis group and in further follow-up in the aortic stenosis and combined disease group. Normalization of left ventricular size is observed in more than 90% of patients during 5-year follow-up as opposed to left ventricular muscle hypertrophy, regressed only in less than a half of the study population. In patients with aortic valve disease the greatest hemodynamic improvement is observed 1 year after valve replacement. This is expressed by marked reduction of the left ventricular dimensions and wall thickness, without significant improvement of the ejection fraction. Further regression of left ventricle dimensions occurs in patients operated on due to predominant valve insufficiency, whereas regression of left ventricular hypertrophy is observed in patients with preexisting valvular stenosis.