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A Schieppati

Publications and source records attributed to A Schieppati.

33 records · Page 2Linked to original sources
PubMed1989

Angiotensin-converting enzyme inhibition ameliorates the defect in glomerular size selectivity in hyponatremic hypertensive syndrome.

The glomerular size-selective properties in a patient with "hyponatremic hypertensive syndrome" were investigated before and after administration of the angiotensin-converting enzyme inhibitor enalapril. Hyponatremic hypertensive syndrome is a rare condition of renovascular hypertension characterized by electrolyte abnormalities (hyponatremia, hypokalemia), polyuria, and high renin activity. In this patient a marked increase in urinary protein excretion was observed. Treatment with enalapril normalized BP, corrected electrolyte abnormalities, and reduced proteinuria. Glomerular filtration rate (GFR), renal plasma flow (RPF), and the clearance of neutral dextrans of graded sizes were measured before and after 6 months of enalapril (20 mg/d) administration. Theoretical analysis of dextran and inulin clearance data with a model of glomerular size selectivity were adopted to separate effects of hemodynamic changes on macromolecule filtration from changes of intrinsic membrane selective properties. After enalapril urinary protein excretion decreased, GFR was unchanged and RPF almost doubled. Fractional clearance values of dextran molecules were markedly elevated in comparison with the corresponding values measured in a group of normal controls and were normalized by enalapril. Theoretical calculation of membrane pore characteristics showed that enalapril treatment reduced the radius of all membrane pores by approximately 1 nm. Altogether these results indicate that enalapril normalized glomerular filtration of neutral macromolecules and circulating proteins in a human condition of angiotensin II-induced proteinuria. Enalapril effectively restored glomerular size-selective function, reducing dimensions of membrane pores, independently of its effect on renal hemodynamics.

Aged↗
PubMed1988

Effect of extracellular acidosis on 45Ca uptake in isolated hypoxic proximal tubules.

Recent in vitro studies have suggested that the presence of extracellular acidosis is protective against the development of oxygen-deprivation injury in several tissues. Because cellular Ca accumulation after renal ischemia may represent a major pathogenic event leading to cellular damage, the purpose of the present study was to examine the effect of extracellular acidosis on 45Ca uptake and desaturation in normal and hypoxic isolated rat proximal tubules. At pH 7.4, an increase in 45Ca uptake was observed in proximal tubules after 30 min of hypoxia. In addition, 45Ca desaturation was increased significantly in hypoxic tubules at pH 7.4. The alterations in 45Ca uptake and desaturation in hypoxic tubules at pH 7.4 were accompanied by significant signs of cellular injury as assessed by the amount of lactate dehydrogenase (LDH) released by the tubules at the end of the hypoxic period (22.5% above control tubules, P less than 0.01) as well as in morphological changes consistent with hypoxic cell injury. In contrast, when maintained at pH 6.9 throughout the study, no difference in 45Ca uptake or desaturation was observed between the control and hypoxic tubules; the hypoxic proximal tubules exhibited a smaller increase in LDH release (12.7% above control tubules) and did not develop the morphological changes observed at pH 7.4. Thus, during hypoxia and reoxygenation at pH 7.4, the increased 45Ca uptake may contribute in part to cellular injury in rat proximal tubules.

Acid-Base Equilibrium↗
PubMed1985

Effect of renal ischemia on cortical microsomal calcium accumulation.

Mitochondrial respiration, Ca2+ content, and Ca2+ kinetics have been found to be profoundly altered in ischemic acute renal failure (ARF). The effect of clamping the bilateral renal artery for 50 and 90 min on microsomal Ca2+ uptake was therefore examined in the rat. The 50-min clamping produced a reversible model of nonoliguric ARF, and the 90-min clamping produced a model of nonreversible oliguric ARF. In the 50-min nonoliguric model, ATP-dependent Ca2+ uptake by microsomes from renal cortex (nmol X mg protein-1 X 30 min-1) was significantly impaired immediately before release of the clamp and before return of renal blood flow (reflow) (191 +/- 11 vs. 83 +/- 11, P less than 0.005). However, in this nonoliguric model of ischemic ARF, microsomal uptake returned completely to normal after 1 h of reflow (sham 189 +/- 11 vs. 167 +/- 14 at 1 h, NS) and persisted at this normal level at 24 h (sham 166 +/- 14 vs. 150 +/- 13 at 24 h, NS). In the oliguric model of ARF the microsomal Ca2+ uptake also was impaired immediately after the clamp release (sham 191 +/- 11 vs. 93 +/- 11, P less than 0.001) as well as after 1 h of reflow (sham 189 +/- 11 vs. 129 +/- 12, P less than 0.005) but not at 24 h (sham 166 +/- 14 vs. 173 +/- 13, NS). The results indicate that impaired microsomal Ca2+ uptake occurs early in both oliguric and nonoliguric ARF and persists after 1 h of reflow in the oliguric model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1985

Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated?

Parathyroid hormone (PTH) is a polypeptide which in different in vitro systems raises intracellular cyclic AMP (cAMP) levels via adenyl cyclase activation and stimulates Ca2+ transport across cell membranes. We tested whether, on the basis of this mechanism, PTH would inhibit human platelet aggregation. The latter was tested in vitro by a photometric technique. Platelet aggregation induced by the calcium ionophore A 23187 was inhibited by PTH at concentrations (0.5-3 USP U/ml) similar to those effective in other in vitro systems. Higher concentrations of PTH were required to prevent aggregation initiated by adenosine-5'-diphosphate, arachidonic acid, or platelet-aggregating factor. The terminal synthetic fragment 1-34 b PTH was ineffective against all aggregation stimuli. The antiaggregating effect of PTH was potentiated by verapamil and theophylline and was additive to that of PGI2. However, PTH did not appear to increase platelet cAMP levels and was not counteracted by an inhibitor of platelet adenyl cyclase. It is therefore unlikely that PTH inhibits platelet aggregation through an adenyl cyclase stimulated increase of cAMP. Since PTH levels are markedly increased in uremic plasma, it might contribute to the defective platelet function and the bleeding tendency frequently occurring in uremic patients.

Adenylyl Cyclases↗
PubMed1984

The metabolism of arachidonic acid by platelets in nephrotic syndrome.

The production of malondialdehyde (MDA) and thromboxane B2 (TxB2) by platelets following an arachidonic acid (AA) challenge was greater in nephrotic platelet rich plasma (PRP) than in normal PRP. The uptake of 14C-AA, and its subsequent conversion to 14C-TxB2 following a thrombin stimulus, was also greater in nephrotic than normal PRP. Normal plasma diminished the MDA production by nephrotic platelets. The addition of albumin to nephrotic PRP, or, the intravenous infusion of albumin in quantities sufficient to correct hypoalbuminemia also diminished the excessive production of prostaglandin metabolites by nephrotic platelets. The platelet aggregate ratio (PAR), which measures circulating platelet aggregates, was abnormal during the acute phase of nephrotic syndrome but reverted to normal following remission. These data indicate that hypoalbuminemia is associated with increased AA metabolism by platelets and suggest that platelet "hyperactivity" may contribute to the proclivity toward thrombosis observed in nephrotic syndrome.

Albumins↗
PubMed1983

Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclooxygenase defect.

A qualitative platelet abnormality and a bleeding tendency are frequently associated with renal failure and uremia. We demonstrated previously that uremic patients display an abnormal platelet aggregation to arachidonic acid and reduced malondialdehyde production in response to thrombin and arachidonic acid. The objectives of this investigation were: (a) to compare platelet prostaglandin (PG) and thromboxane (TX) production in whole blood and in platelet-rich plasma (PRP) of 21 uremic patients and 22 healthy subjects; (b) to evaluate the concentration and activity of platelet PG- and TX-forming enzymes; (c) to assess the functional responsiveness of the platelet TXA(2)/PGH(2) receptor; (d) to explore the hemostatic consequences of partially reduced TXA(2) production.Platelet immunoreactive TXB(2) production during whole blood clotting was significantly reduced, by approximately 60%, in uremic patients as compared to age- and sex-matched controls. Exogenous thrombin (5-30 IU/ml) failed to restore normal TXB(2) production in uremic platelets. Uremic PRP produced comparable or slightly higher amounts of TXB(2) than normal PRP at arachidonate concentrations 0.25-1 mM. However, when exposed to substrate concentrations >2 mM, uremic PRP produced significantly less TXB(2) than normal PRP. To discriminate between reduced arachidonic acid oxygenation and altered endoperoxide metabolism, the time course of immunoreactive TXB(2) and PGE(2) production was measured during whole blood clotting. The synthesis and release of both cyclooxygenase-derived products was slower and significantly reduced, at all time intervals considered. Furthermore, PGI(2) production in whole blood, as reflected by serum immunoreactive 6-keto-PGF(1alpha) concentrations, was significantly reduced in uremic patients as compared with healthy subjects. PGH synthase levels, as determined by an immunoradiometric assay, were not significantly different in platelets from uremic patients as compared to control platelets. A single 40-mg dose of aspirin given to five healthy volunteers reduced their serum TXB(2) to levels found in uremic patients. This was associated with a significant increase of threshold aggregating concentrations of ADP and arachidonic acid and prolongation of bleeding time. Substantially similar threshold concentrations of U46619, a TXA(2) agonist, induced aggregation of normal and uremic platelets. Prostacyclin induced a significant elevation of uremic platelet cyclic AMP, which was suppressed by U46619, further suggesting normal responsiveness of the TXA(2)/PGH(2) receptor. WE CONCLUDE THAT: (a) an abnormality of platelet arachidonic acid metabolism exists in uremia, leading to a reduced TXA(2) production; (b) the characteristics of this abnormality are consistent with a functional cyclooxygenase defect; (c) reduced TXA(2) production may partially explain the previously described abnormality of platelet function in uremia.

Adult↗
PubMed1982

Platelet function in patients on maintenance hemodialysis: depressed or enhanced?

Uremic patients on long-term hemodialysis show a paradoxical association of hemorrhages on the one hand and thrombotic complications or atherosclerosis on the other. Platelet function has been found to be depressed in some cases but enhanced in others. In 19 patients, both platelet aggregation and prostaglandin formation appeared to be significantly enhanced in response to low concentrations of arachidonic acid but significantly reduced with high concentrations. It is suggested that this double functional abnormality of uremic platelets may contribute to the complex vascular disturbances of hemodialyzed patients.

Arachidonic Acids↗
PubMed1981

Plasmatic regulation of vascular prostacyclin in pregnancy.

Activity of prostacyclin-stimulating factor was measured in six normal, non-pregnant women, six women in early normal pregnancy, six in late normal pregnancy, and six in late pregnancy complicated by severe pre-eclampsia. The activity was lower in the women in late pregnancy than in those in early pregnancy and the controls but was about normal in those with severe pre-eclampsia. These results may be relevant to the physiology of pregnancy and the pathogenesis of pre-eclampsia.

Adolescent↗
PubMed1979

Prostacyclin and human foetal circulation.

Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.

Adolescent↗