Search PubMed⌕ Search

Biomedical subjects

F A Carone

Publications and source records attributed to F A Carone.

At least 91 records · Page 5Linked to original sources
PubMed1978

Effects of constituent amino acids on tubular handling of microinfused angiotensin II.

[14C]angiotensin II ([14C]AII) was microinjected alone or with excess L-isoleucine (IIe) or L-aspartic acid (Asp) into renal tubules of anesthetized rats. Urinary excretion of 14C-labeled material was measured, and the intact peptide and its metabolites were identified and quantified. When isoleucine was administered with [14C]AII, urinary recovery of the 14C-labeled material increased directly with distance of infusion site from glomerulus, and most of the radioactivity in urine was [14C]Ile. The data suggest that isoleucine interfered with reabsorption of [14C]Ile derived from hydrolysis of [14C]AII and less so with the hydrolysis itself. When aspartic acid was administered with [14C]AII into the proximal 5/6 of the proximal convolution, total urinary recovery of the 14C-labeled material was unchanged, but percentage of recovery as [14C]AII increased; with infusion into the distal 1/6 of the proximal convolution, total urinary recovery of the 14C labele increased. The data suggest that aspartic acid interfered with the enzymatic hydrolysis of [14C]AII and reabsorption of isoleucine. In distal tubules the 14C label was almost completely recovered as intact [14C]AII in all protocols. The results show that free amino acids influence proximal tubular handling of small linear peptides in rats.

Angiotensin II↗
PubMed1977

Handling of angiotensin II and oxytocin by renal tubular segments perfused in vitro.

In order to study renal tubular handling of two small peptide hormones, [14c]angiotensin II ([14C]AII) and [3H]oxytocin ([3H]OT) were microperfused through rabbit kidney tubule segments in vitro. The reabsorption and tubular sequestration of radioactive label were determined, and the collection fluid was electrophoretically analyzed. The data suggest that [14C]AII is extensively hydrolyzed in the pars recta of the nephron and is rapidly reabsorbed across the tubular epithelium. Under similar experimental conditions, hydrolysis of [3H]OT was not observed in either the proximal straight or cortical collecting tubule segment, and the rate of reabsorption was low. Thus, tubular handling of OT appears to differ from that of AII, probably because of differences in molecular structure.

Angiotensin II↗
PubMed1977

The pharmacology and subacute toxicology of dopamine.

Preclinical studies with dopamine showed a unique spectrum of biological activities which suggested that it might be of therapeutic use in the clinical syndromes of shock and low cardiac output. Most prominent among these were its effects on cardiac output, renal perfusion, and vital organ flow. The unique effect on renal function and the subsequent studies by Goldberg and his colleagues led to the recognition of a previously unknown catecholamine receptor site, the 'dopaminergic receptor'. Studies on the toxicology of dopamine in our laboratories suggested that dopamine could be safely used in the clinic.

Animals↗
PubMed1976

Micropuncture evidence of rapid hydrolysis of bradykinin by rat proximal tubule.

3H-labeled bradykinin ([3H]BKN) and 14C-labeled inulin ([14C]In) were simultaneously microinfused into proximal or distal tubules in Inactin-anesthetized rats, and urinary excretion and tubular transit times were measured. In other experiments higher doses of [3H]BKN were microinfused and intact peptide and its metabolites identified and quantified by two-dimensional peptide mapping. The site of infusion was identified by neoprene injection and microdissection. Urinary recovery of 3H label was 24.1% when proximal tubules were infused and 98.0% when distal tubules were infused. For proximal tubules, 85% of 3H activity recovered from urine consisted of metabolites (81%[3H]Pro and 4% [3H]Arg1-Phe5) and 15% was intact BKN. Urinary recoveries of [3H]BKN and metabolites were unrelated to tubular length. With distal tubules all 3H activity appeared as intact BKN. Excretion curves of simultaneously infused [3H]BKN and [14C]In showed no marked differences in configuration for either proximal or distal or distal tubules. We suggested that removal of [3H]BKN by proximal tubular cells occurs by rapid enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder.

Animals↗
PubMed1976

Inhibition of proximal tubular hydrolysis and reabsorption of bradykinin by peptides.

[3H] bradykinin ([3H] BKN) was microinfused alone or in the presence of a 390- or 780-fold excess of BKN or angiotensin I (AI) into proximal tubules in Inactin-anesthetized rats. Urinary excretion of 3H-labeled material was measured, and intact peptide and its metabolites were identified and quantified. When [3H] BKN was administered with BKN or AI, urinary recovery of 3H-labeled material was increased in a manner directly proportional to tubular length, suggesting that reabsorption of [3H] BKN is related to extent of tubular contact. BKN and AI were equally effective in inhibiting the reabosroption of [3H] BKN and its metabolites from proximal tubular fluid. In contrast, BKN but not AI effectively inhibited the enzymatic hydrolysis of [3H] BKN in the proximal tubule, The data suggest that the proximal tubular mechanism for reabsorbing BKN and its metabolites is of high capacity but not high specificity and that the mechanisms for enzymatic cleavage and reabsorption of BKN and its metabolites may had different specificites and capacities.

Angiotensin II↗
PubMed1975

Fate of labeled angiotensin II microinfused into individual nephrons in the rat.

14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder

Angiotensin II↗
PubMed1975

Effects of renal lymphatic occlusion and venous constriction on renal function.

The effects of renal lymphatic occlusion or increased lymph flow due to renal vein constriction on renal function were investigated in rats. In each experiment, the renal lymphatics or vein of the left kidney were occluded or constricted and the right kidney served as a control. Occlusion of renal lymphatics caused renal enlargement, no change in glomerular filtration rate, a marked increase in urine flow and solute excretion without any change in urine osmolality, and enhanced urinary loss of urea, potassium, sodium and ammonium. Urea concentrations in medullary and papillary tissues were significantly elevated. Renal vein constriction caused renal enlargement and a marked drop in glomerular filtration rate, urine volume, urine osmolality and solute excretion. tissue concentrations of urea and potassium were decreased in the medulla and papilla and total tissue solute was significantly decreased in the papilla. The data indicate that in the rat, renal lymphatic occlusion traps urea in the medulla and induces a urea diuresis resulting in a large flow of normally concentrated urine. On the other hand, increased lymph flow secondary to renal vein constriction decreases medullary urea and potassium concentrations and papillary osmolality. These changes and the reduced glomerular filtration rate result in a small flow if dilute urine. Thus both renal lymphatic occlusion and enhanced lymph flow have a significant effect on renal function.

Ammonia↗
PubMed1975

Cystic disease of the renal medulla associated with retinitis pigmentosa and imino acid abnormalities.

A 22 year old man with renal failure associated with salt wasting, retinitis pigmentosa, and imino acid abnormalities is reported. Renal tissue showed changes compatible with medullary cystic disease or juvenile nephronophtisis. Special studies were carried out to clarify the mechanism of renal salt wasting. Retinal pigmentary changes were found in three siblings and a male cousin; in two siblings studied abnormal retinal function was demonstrated. the parents who were first cousins once removed were normal. Fifty kindred members were examined and none showed unequivocal signs of renal disease. Autosomal recessive transmission of ocular and renal disease appeared likely. The separation of medullary cystic disease from juvenile nephronophthisis on the basis of onset and mode of inheritance is probably artificial.

Adult↗
PubMed1975

Acute calcium nephrotoxicity. An electron microscopical and semiquantitative light microscopical study.

Rats were infused for three hours with doses of calcium gluconate to elevate serum calcium level and were killed either immediately after infusion or after 24 hours. Necrosis of proximal tubular cells was observed when serum calcium level was 16.0 mg/dl or higher. Above 16.0 mg/dl, an additional 5% of renal tubular profiles contained damaged cells for each 1 mg/dl in serum calcium. No difference in extent of damage was found in rats killed immediately or after 24 hours. Initial changes were formation of granular dense bodies in mitochondria, cell swelling, rupture, and extensive mitochondrial calcification. Renal tubular basement membrane changes appeared to be initiated by protrusion of cytoplasmic buds, forming ovoid bodies, which became embedded in the basement membrane. These ovoid bodies then appeared to serve as a nidus for further extensive basement membrane calcification.

Acute Disease↗
PubMed1975

D-serine nephrotoxicity. The nature of proteinuria, glucosuria, and aminoaciduria in acute tubular necrosis.

Administration of D-serine to rats induced acute necrosis of the proximal straight tubules, proteinuria, glucosuria, and aminoaciduria. Proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by new epithelium. Our findings suggest (1) that abnormal loss of protein and glucose in urine is due to diffusion of these substances from interstitium to tubular fluid across the denuded permeable basement membranes of the necrotic tubules, and (2) that tubular cells normally are a barrier to diffusion of certain solutes betweeen interstitial and tubular fluids. Amino-aciduria preceded the onset of tubular necrosis and increased excretion of some amino acids persisted after tubular repair. Thus, D-serine-induced aminoaciduria may be due to impaired reabsorption of amino acids by the injured proximal straight tubules, as well as by backward diffusion of amino acids from the interstitium.

Acute Kidney Injury↗
PubMed1974

The nature of D-serine--induced nephrotoxicity.

Renal structural changes were studied sequentially between 1 hour and 6 days in rats treated with D-serine. Extensive necrosis of proximal straight tubules was rapid in onset and was followed by complete tubular regeneration 6 days post-treatment. The apparent progression of cellular changes was initial shrinkage, followed either by swelling and loss of apical cytoplasm or immediate lysis of cytoplasmic and nuclear contents. Tubular damage left only the basement membrane as a barrier between interstitial and luminal fluids. In similarly treated rats, proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by epithelium suggesting that they are due to diffusion of protein and glucose from interstitium into tubular fluid across the denuded basement membranes and that epithelial cells, under normal conditions, act as a barrier to diffusion of certain substances between the interstitium and tubular fluid.

Acute Kidney Injury↗
PubMed1973

Adrenal corticosteroid-induced renal cystic disease in the newborn hamster.

A new model of renal cystic disease was developed in newborn Syrian hamsters by the repeated injection of 9-fluoroprednisolone acetate (9-FPA), a long-acting adrenal corticosteroid. Kidneys harvested from the tenth to the fourteenth day of age showed diffuse cystic dilatation of nearly all cortical convoluted tubules. Microdissection revealed that cystic changes primarily involved proximal convoluted tubules and, to a lesser degree, the distal tubules. Electron microscopy showed immaturity of development and varying degrees of degeneration of the cells of the proximal convoluted tubule. Intraluminal obstruction was not detected and therefore could not account for the cystic changes. Analysis of electrolytes in serum and selected tissues showed a significant reduction in potassium and sodium of serum, and significant depletion of potassium, magnesium and calcium in the skeletal muscle. Thus, there was no direct relationship between an electrolyte deficiency and the cystic changes.

Animals↗