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Biomedical subjects

G Malnic

Publications and source records attributed to G Malnic.

108 records · Page 6Linked to original sources
PubMedDate not supplied

Combined in vivo and in vitro approaches to analysis of renal tubule function.

The study of renal tubule function obtained its first impulse with whole kidney approaches, such as the clearance technique, and is presently centered on cellular analysis involving intracellular ion activities and on molecular studies describing the structure of transporter molecules and the function of their subunits and constitutional building blocks as well as their distribution along the nephron and within individual cells. Between these extremes a number of successful techniques have dominated the field, including the micropuncture methods which were pioneered by Richards, Walker and others in the late 1920s and 1930s, and were revived and perfectioned in the following decades leading to complex in vivo and in vitro micromethods that for an important period of time have been the center of scientific progress in this area. In the present paper, some of the methods in this field are shortly reviewed, specifically from the point of view of acid-base physiology applied to the renal tubule.

Animals↗
PubMedDate not supplied

Cisplatinum-induced lesion of proximal tubule acidification in the rat.

Rats were given a 4- to 6-mg/kg body weight intraperitoneal injection of the antitumor drug, Cisplatin, 5-7 days prior to experiments to study tubule acidification by clearance and stationary microperfusion techniques. Cisplatin reduced the glomerular filtration rate markedly and caused a moderate degree of metabolic acidosis, but urine acidification (pH) was well maintained. Proximal tubule stationary pH and bicarbonate concentrations, as measured by pH microelectrodes, were significantly increased. The defect of proximal H+ secretion is reflected by increased acidification half-times (from 4.44 to 10.2 s) and reduced bicarbonate reabsorption to 37% of control values. H-ion back flux, measured during tubule and capillary perfusions with Ringer's bicarbonate- and CO2-free phosphate solutions, was reduced to 68% of control values. The apparent H-ion permeability was lowered from 0.79 to 0.54 cm/s. These results indicate that proximal acidification is reduced by impairment of H+ transport and not by increased transepithelial H+ shunting. Blunted acidification is compatible with a reduction in the number of Na/H exchangers in the proximal brush border and/or a decrease in the apical sodium gradient, the driving force for proximal H-ion secretion. Cortical distal tubule acidification, measured by double-barreled ion-exchange resin/PD microelectrodes, was not significantly affected by Cisplatin. This accounts for the observation that, in spite of the impaired proximal acidification, urine pH is kept within the normal range.

Acid-Base Equilibrium↗
PubMedDate not supplied

Proximal Na+, fluid and HCO3- reabsorption in uninephrectomized rats after a saline load.

We studied the effect of a saline load on proximal tubular Na+, fluid and HCO3- handling of control and uninephrectomized (UNx) rats. Glomerular filtration rate (GFR) was measured by inulin clearance, Na+ reabsorption in the proximal tubule by lithium clearance (CLi+), proximal tubule fluid reabsorption (Jv) by microperfusion with 14C inulin and proximal tubule HCO3- reabsorption (JHCO3-) by estimating pH of perfusate and collected fluid in vitro under CO2 equilibrated oil by means of Sb microelectrodes. No significant differences were found between control and UNx animals in baseline values of urine flow, GFR, fractional water and sodium excretion and blood and urine pH and pCO2, showing that renal function was compensated 4 weeks after UNx. On the other hand, UNx rats showed a significant increase in proximal tubule Jv and JHCO3-. After extracellular fluid volume expansion (EFVE) by infusion of HCO3- Ringer solution (0.1 ml/min) during 90-120 min, in both groups of animals hematocrit decreased by 15%, GFR remained unchanged and fractional Na+ and water excretion increased significantly. However, after EFVE Jv and JHCO3- decreased significantly in control rats but were not modified in UNx animals. Fractional proximal Na+ reabsorption as measured by CLi+ decreased in control rats after EFVE and was not altered in UNx rats. After EFVE the fall in fractional distal Na+ reabsorption was significantly higher in control than in UNx rats. The present results provide evidence that after a saline load the impaired natriuretic response in UNx rats could be attributed to an alteration in proximal and distal tubular Na+ and HCO3- handling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of luminal calcium on proximal tubule bicarbonate reabsorption in the rat.

In previous investigations, it was found that rats depleted in parathyroid hormone (TPTX rats) had reduced rates of proximal bicarbonate reabsorption independent on blood calcium levels. In the present work, the role of calcium (Ca2+) in rat proximal tubule bicarbonate reabsorption was studied by in vivo stationary microperfusion. Tubules were perfused at different lumen Ca2+ concentrations in the presence and absence of the calcium ionophore A23187. Bicarbonate reabsorption was not affected by Ca2+ in the range of 0 to 1 mM, but was significantly reduced when 0.5 mM EGTA was added to the 0 Ca2+ perfusates, indicating that only at very low luminal Ca2+ levels, bicarbonate reabsorption ( = H+ secretion) was impaired. These observations indicate that Ca2+ in the tubule lumen is important for the maintenance of normal proximal bicarbonate transport, but the low Ca2+ level necessary to impair this transport mechanism is achieved only in the presence of EGTA, a condition that simulates the absence of parathyroid hormone.

Absorption↗
PubMedDate not supplied

Role of the kidney in controlling acid-base balance.

The kidney is responsible for the maintenance of an important sector of the regulation of acid-base balance, i.e., that related to the maintenance of the alkaline reserve of the body and to excretion of fixed acids. In this review, the basic mechanisms of H-ion secretion along the nephron, responsible for bicarbonate reabsorption, titratable acid formation and ammonia excretion, are discussed. The mechanisms responsible for tubule acidification along proximal tubule, thick ascending limb, cortical distal tubule and collecting duct are reviewed, having in mind the function of the apical and basolateral membranes. Finally, the pathophysiological aspects of urinary acidification are discussed, focusing on renal tubular acidosis models (induced by maleate and amphotericin B treatment) and their cellular mechanisms, as well as the role of adrenal steroids in urinary acidification.

Acid-Base Equilibrium↗