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C L Chou

Publications and source records attributed to C L Chou.

68 records · Page 4Linked to original sources
PubMed1990

Concentration dependence of urea and thiourea transport in rat inner medullary collecting duct.

The vasopressin-dependent urea permeability of the rat terminal inner medullary collecting duct (IMCD) is much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of vasopressin-stimulated facilitated transport pathway. We used the isolated perfused tubule technique to test whether the urea transport pathway exhibits saturation characteristics consistent with a facilitated pathway. When the luminal urea concentration was varied between 0 and 800 mM (no urea in peritubular bath), the relationship between the urea flux and the luminal concentration was linear with a y-axis intercept that was not significantly different from zero, indicating an absence of saturation in this concentration range. Higher concentrations of urea could not be tested due to technical limitations. However, when thiourea (a urea analogue that shares the urea transport pathway with urea) was substituted for urea in similar experiments, the apparent thiourea permeability fell with increasing thiourea concentration in the range 10-200 mM, indicative of saturation of the urea-thiourea transporter. When the urea concentration was varied in both bath and lumen, the lumen-to-bath urea flux approached a limiting value at 400-500 mM urea, consistent with saturation of the transporter. However, nonspecific inhibition of urea transport by bath urea could not be ruled out in those experiments. We conclude that the urea and thiourea transport pathway in the terminal IMCD exhibits saturation characteristics. However, the urea concentration required to saturate the pathway is apparently high, at least 400-500 mM in one set of experiments and probably greater than 800 mM in another.

Animals↗
PubMed1990

Urea gradient-associated fluid absorption with sigma urea = 1 in rat terminal collecting duct.

It has been proposed that inner medullary collecting ducts (IMCDs) can absorb fluid in the absence of a transepithelial osmolality gradient if a perfusate-to-bath urea gradient is present. Such a process has been suggested to be caused by a nonunity reflection coefficient for urea (sigma urea less than 1). However, our recent measurements of sigma urea yielded values not significantly different from 1.0. The present study was done to readdress the possibility of direct coupling of water and urea transport in the rat IMCD. Isolated rat terminal IMCD segments were studied in the presence of 10(-10) M vasopressin with the osmolality of the perfusate equal to that of the peritubular bath but with a perfusate-to-bath urea gradient (bath osmolality balanced with NaCl). We measured both fluid absorption rate and urea concentration in collected fluid and calculated the osmolality of the collected fluid. We observed rapid fluid absorption associated with substantial urea absorption. The urea absorption caused a large fall in the osmolality of the collected fluid with respect to the bath. Simulations with a mathematical model of an isolated perfused tubule revealed that the transepithelial osmolality gradient generated along the length of tubule (caused by urea absorption) was large enough to account for the fluid absorption. Measurement of sigma urea with the "zero-flux" (or null point) method revealed a value of 1.00 +/- 0.02. Thus we conclude that the observed fluid absorption is the result of a transepithelial osmolality gradient generated by rapid urea absorption and does not require sigma urea less than one.

Absorption↗
PubMed1990

The protective effect of mepacrine on acute lung edema induced by phorbol myristate acetate in rats.

A good model of adult respiratory distress syndrome is lung injury induced by phorbol myristate acetate (PMA). In the present study we examined the effect of mepacrine, an inhibitor of phospholipase A2, on lung injury induced by PMA in isolated blood-perfused rat lungs. In the isolated lung, saline (1 ml) or mepacrine (75 microM) alone in the perfusion system did not discernibly change the pulmonary arterial pressure (PAP) and lung weight (LW). After administration of PMA (0.16 micrograms/ml), severe hypertension and lung edema developed (delta PAP = 40.1 +/- 6.0 mmHg, p less than 0.001; delta LW = 5.5 +/- 0.7 g, p less than 0.001). Whereas, the addition of mepacrine (75 microM) prevented PMA-induced lung edema and pulmonary hypertension (delta PAP = 4.7 +/- 2.2 mmHg, delta LW = 0.2 +/- 0.2 g). To further elucidate the protective mechanism of mepacrine on lung injury, a vasodilator (nitroprusside) was given to decrease PAP levels to +6 mmHg from baseline values in the PMA group, as well as in the mepacrine-pretreated PMA (MPMA) group. During a subsequent venous pressure challenge, severe lung injury developed in the PMA group (delta LW = 9.5 +/- 2.1 g, p less than 0.001). However, with the same venous pressure challenge in the MPMA the lung weight was markedly less than that of the PMA group (delta LW = 1.0 +/- 0.2 g). Histologic findings examined by light microscopy presented intraalveolar hemorrhage and fluid accumulation, disruption of vascular basements and alveolar septa, and aggregation of inflammatory cells within the parenchyma in the lungs of the PMA group. In the MPMA group there was no evidence of intraalveolar hemorrhage and alveolar fluid accumulation, however, the occasional presence of granulocytes in the parenchyma and slight interstitial edema were still observed. In addition, depressed the chemiluminescence release from PMA activated granulocytes which were in a dose-dependent manner in vitro. These observations suggest that mepacrine inhibits PMA-induced lung injury chiefly by protection of vascular permeability. The mechanism of the protection may be due to the inhibition of oxygen radicals released from activated neutrophils and the reduction of neutrophil chemotaxis.

Animals↗
PubMed1990

Dimethylthiourea decreases acute pulmonary edema induced by phorbol myristate acetate in isolated blood-perfused lung of the rat.

Acute pulmonary edema can be induced by phorbol myristate acetate (PMA). Oxygen radicals released from the neutrophils have been considered to play an important role in the pathogenesis of PMA-induced pulmonary edema. In the present experiment, we studied the effect of dimethylthiourea (DMTU) on PMA-induced pulmonary injuries in isolated perfused lungs of rats. DMTU is a potent scavenger of the hydroxyl radical and hydrogen peroxide. PMA infusion into the isolated lung increased pulmonary arterial pressure (delta PAP) by 37.8 +/- 3.9 mmHg. The lung weight gain (LWG) and lavage albumin concentration (LAC) amounted to 6.2 +/- 1.2 g and 102.0 +/- 22.9 mg/dl, respectively. DMTU (100 mM) pretreatment significantly reduced the PAP increase (delta PAP = 4.6 +/- 0.8 mmHg, p less than 0.001), LWG (0.3 +/- 0.1 g, p less than 0.01) and LAC (25.3 +/- 1.7 mg/dl, p less than 0.01). Additional in vitro experiments demonstrated that DMTU depressed the chemiluminescence released from neutrophils activated by PMA (17.9 +/- 2.6 mV.min to 2.6 +/- 0.5 mV.min, p less than 0.01). The results suggest that DMTU, a scavenger of toxic radicals, decreases the lung edema through both attenuation of pulmonary hypertension and protection of vascular permeability from PMA injury.

Acute Disease↗
PubMed1989

Independence of urea and water transport in rat inner medullary collecting duct.

Several published models of the renal concentration mechanism have assumed a reflection coefficient for urea in the inner medullary collecting duct (IMCD) that is less than unity, implying direct coupling between water and urea transport. In the present study, we used isolated perfused terminal IMCD segments and mathematical modeling of IMCD transport to determine the validity of this assumption. Mathematical simulations of IMCD transport, using recently published data on urea and water permeability, revealed that the method previously used to measure the reflection coefficient for urea underestimates the true value. The modeling results allowed us to design two new experimental protocols to determine the reflection coefficient for urea. In the first protocol, we measured the ability of a transepithelial urea gradient to induce a water flux, correcting for the dissipation of the urea gradient by rapid passive urea permeation. In the second protocol, we directly measured the solvent drag of urea resulting from an osmotically induced water flux. Both protocols yielded values for the urea reflection coefficient that were not significantly different from unity (0.92 +/- 0.04 and 1.07 +/- 0.05, respectively). Thus we find no evidence for direct coupling between urea and water transport in the rat terminal IMCD.

Animals↗
PubMed1989

Inhibition of urea transport in inner medullary collecting duct by phloretin and urea analogues.

Arginine vasopressin (AVP) increases the urea permeability of the rat terminal inner medullary collecting duct (IMCD) to levels much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of an AVP-stimulated facilitated transport pathway. We tested whether inhibitors of facilitated urea transport in erythrocytes and toad bladder also inhibit urea transport in the isolated perfused IMCD. Apparent urea permeability (Purea) was determined by measuring the flux due to an imposed 5 mM concentration gradient. Phloretin (0.25 mM in lumen or bath) reversibly inhibited Purea. Phloretin, however, did not alter the osmotic water permeability. Urea analogues (200 mM) in the bath inhibited Purea (thiourea, 74% inhibition; methylurea 65%; acetamide 35%). Urea analogues in the lumen decreased Purea with the same order of potency. The inhibitory K1/2 for thiourea in the lumen was 27 +/- 2 mM and did not change with 10(-10) M AVP (28 +/- 3), despite a fourfold increase in Purea. We conclude the following. 1) Inhibitor actions on urea transport in the IMCD are similar to those in red blood cells and toad bladder, suggesting that the urea transporter could be a membrane protein similar to that in the other tissues. 2) Inhibition of Purea by phloretin without an effect on vasopressin-stimulated water permeability supports the view that the urea pathway is not the vasopressin-stimulated water channel. 3) The ability of AVP to increase Purea without an effect on the inhibitory K1/2 for thiourea indicates that AVP probably does not act by altering the binding affinity of individual transporters for urea.

Amiloride↗
PubMed1988

Time course of proximal tubule response to acute arterial hypertension in the rat.

Acute hypertension was previously shown to cause partial inhibition of proximal tubule fluid reabsorption in perfused tubules in the rat. If the inhibition also occurs in unobstructed tubules receiving native glomerular filtrate, hypertension should increase end proximal flow rate despite autoregulation of glomerular filtration rate (GFR). We tested this prediction with a videodensitometric method recently developed for measurement of tubular flow rate that does not interrupt flow to the macula densa. Hypertension was induced by increasing total peripheral resistance in rats receiving several hormones at rates designed to maintain high levels of these agents. End proximal flow rate was increased 18% as early as 1.5-2 min following the induction of hypertension and increased over the course of the next 25-30 min to reach values 50% greater than controls as the hypertension was sustained. Whole-kidney GFR and renal blood flow were fully autoregulated. The results confirm that hypertension increases the fluid load to the loop of Henle, and are consistent with an effect on proximal tubule fluid reabsorption. This increase in fluid load could signal the macula densa and contribute to the efficacy of autoregulation; it could also provide a significant fraction of the increased fluid and salt excretion of pressure natriuresis.

Acute Disease↗
PubMed1987

Measurement of flow rate in rat proximal tubules with a nonobstructing optical method.

A method was developed for measuring volume flow rate in free-flowing proximal tubules. Multiple injections of a solution containing fluorescein isothiocyanate-dextran (mol wt 20,000) were made into the tubular fluid stream while fluorescence was detected by videomicroscopy. Progression of the dye bolus between two points along the tubule was measured to determine fluid velocity. Tubule diameter was measured by video image shearing and flow rate was calculated from the product of velocity and cross-sectional area. The technique was validated by simultaneous collections in the same tubule just downstream. There was good correlation between the results obtained with the two methods (r = 0.89). The estimated average injection volume was 0.0165 +/- 0.00016 nl. An increase in tubular volume flow caused by repetitive injections during micropuncture collections was too small to be detected. This new method should be useful in experimental situations that require uninterrupted delivery of fluid to the macula densa, or when better temporal resolution is required than can be obtained with the conventional method.

Animals↗
PubMed1986

Role of proximal convoluted tubule in pressure diuresis in the rat.

The role of different nephron segments in the diuretic response to acute arterial hypertension was studied with tubular microperfusion. Early proximal convolutes were perfused with synthetic glomerular ultrafiltrate; fluid was collected from the last visible loop of the same proximal or from the first loop of the distal tubule. In late proximal collections, an increase of arterial pressure of 24 +/- 2 mmHg reduced reabsorption of tubular fluid 44 +/- 4%. Perfusate chloride concentration fell, but only 2 meq/liter, so that chloride reabsorption was inhibited in proportion to the inhibition of fluid reabsorptions, with a corresponding increase in chloride delivery to the loop of Henle. In early distal collections, there was no significant difference of the early distal flow rate with hypertension, but early distal chloride concentration increased 31 +/- 8% and chloride load increased 45 +/- 12%. Qualitatively similar increases were obtained from paired collections made from free-flowing early distal tubules. Inhibition of proximal fluid reabsorption is a primary response to acute hypertension and may contribute to pressure diuresis. In addition, this inhibition increases the strength of the luminal signal to the macula densa, enhancing the autoregulatory response to hypertension.

Absorption↗
PubMed1986

Intrarenal mechanisms mediating pressure natriuresis: role of angiotensin and prostaglandins.

The ability of the kidney to increase sodium and water excretion in response to increases in perfusion pressure has been recognized for more than 50 years. Because glomerular filtration rate is tightly autoregulated, pressure natriuresis occurs as the result of decreased tubular sodium reabsorption rather than increased filtered load. Micropuncture and microperfusion data support the contention that acute changes in arterial pressure can alter proximal tubule reabsorption; however, studies have failed to show a consistent association between changes in sodium excretion and peritubular, interstitial, or tubular pressures. Thus, the specific intrarenal mechanism for the change in tubular reabsorption in response to an acute change in arterial pressure does not appear to be related to the peritubular physical factors at the level of outer cortical nephrons. The possible roles of angiotensin and prostaglandins as humoral mediators of pressure natriuresis are considered in this report. Although angiotensin II is a powerful modulator of the slope of the pressure natriuresis relationship, the responsiveness of sodium excretion to arterial pressure is actually enhanced by angiotensin-converting enzyme inhibitors. These data suggest that angiotensin does not mediate the basic phenomenon. Recent experiments indicate that intrarenal prostaglandins also modulate the magnitude of the pressure natriuresis relationship, but these hormones do not appear to be essential for its basic manifestation.

Absorption↗
PubMed1981

Auditory brainstem potentials in chronic alcoholics.

Auditory brainstem potentials were recorded from abstinent chronic alcoholics and control subjects. The latencies of peaks II, III, IV, and V were significantly delayed in the alcoholic patients compared to control subjects. Brainstem transmission time was longer in alcoholics than in controls. This study provides systematic evidence that chronic alcohol abuse results in brainstem deficits suggesting possible demyelination of auditory tracts.

Adult↗