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Biomedical subjects

M Cirillo

Publications and source records attributed to M Cirillo.

At least 91 records · Page 5Linked to original sources
PubMed1990

Reduced calcium binding capacity is an intrinsic abnormality of red blood cell membrane in spontaneously hypertensive rats.

Reduced calcium (Ca) binding capacity is a widespread and primary abnormality in SHR. It was reported that in red blood cell (RBC) membranes it is detectable only in membrane preparations containing sealed inside-out vesicles, the formation of which implies the partial removal of cytoskeletal proteins from the RBC membrane. The present study compares the Ca binding capacity of RBC membrane preparations with normal (+CS) and reduced (-CS) cytoskeleton content in SHR and normotensive WKY control rats. In addition to Ca binding capacity and protein content, the cholesterol content and the acetylcholinesterase (ACE) activity were measured as having a quantitative measure of integral membrane components in the different membrane preparations. In both strains the cholesterol/protein ratio, the ACE activity per mg of membrane protein, and the Ca binding capacity were all significantly higher in -CS compared to +CS membrane preparations (P less than .001). A statistically significant difference in Ca binding capacity between SHR and WKY was observed only using -CS membranes preparation. The results support the concept of a reduced membrane Ca binding capacity in rat genetic hypertension: this abnormality is detectable only in membrane preparations with reduced cytoskeletal content.

Acetylcholinesterase↗
PubMed1989

On the pathogenetic mechanism of hypercalciuria in genetically hypertensive rats of the Milan strain.

The aim of this study was to investigate the pathogenesis of hypercalciuria in the Milan strain of genetically hypertensive rats. Dietary calcium intake and urinary and fecal calcium output were measured simultaneously with indices of sodium and phosphate homeostasis in male rats of the Milan hypertensive and normotensive strains. In addition, urinary calcium and creatinine excretion rates, calcium, phosphate and creatinine serum concentrations, and bone calcium content were also measured in these rats after an overnight fast. Under fed steady-state conditions dietary calcium, sodium, and phosphate intakes, were similar in the two groups of rats, but hypertensive rats had twofold higher urinary calcium excretion and normal urinary excretion of sodium and phosphate. Fecal calcium output was slightly but significantly higher in the adult hypertensive rats while fecal sodium and phosphate excretion was normal. Because of increased urinary and fecal calcium loss, net calcium balance was significantly less positive in hypertensive than in control rats. Under fasting conditions hypertensive rats were confirmed to have hypercalciuria despite normal serum calcium concentrations and normal creatinine clearance. In accordance with balance data and fasting hypercalciuria, bone calcium content was found to be significantly reduced in hypertensive rats. These findings confirm that hypercalciuria in the Milan hypertensive rats is explained by an altered renal calcium handling; it is also associated with a slightly increased fecal calcium output and, therefore, with a less positive calcium balance and reduced bone calcium content.

Animals↗
PubMed1989

Erythrocyte and platelet volume in human hypertension. The Gubbio Study Collaborative Group.

It has been reported that in rat and human hypertension the erythrocyte volume is reduced while platelet volume is increased. Data from the Gubbio Study, a population-based study involving over 5000 people (response rate greater than 84%), were analysed in order to address this issue among adult participants. The erythrocyte volume was significantly greater in male and female hypertensives compared with sex-matched normotensives. Female hypertensives also had a slightly but significantly reduced platelet volume while no significant difference in platelet volume was found between male hypertensives and male normotensives. Contrary to data from previous clinical studies based on small series of patients and controls, the findings of this study indicate a positive association between hypertension and erythrocyte volume.

Aging↗
PubMed1989

Calcium binding capacity of erythrocyte membrane in human hypertension.

The cell membrane calcium binding capacity of genetically hypertensive rats is reduced when measured in the presence of the submicromolar calcium concentrations proper of intracellular environment. The present work, performed as an ancillary study to an epidemiological survey on an entire population, aimed to investigate the existence of a similar abnormality in human hypertension. Calcium binding to the erythrocyte membrane was measured in clinically healthy normotensive (n = 12) and hypertensive individuals (n = 24). For this purpose, a filtration technique was used, based on the determination of 45Ca bound to the erythrocyte membrane in the presence of free calcium concentrations (40 nmol/l and 1 mumol/l), which are similar to those of the intracellular environment. The intra-assay technical error was determined on 35 duplicate samples and, when expressed as percent of the mean, was 24.1 at the 40 nmol/l concentration and 16.8 at the 1 mumol/l concentration. Membranes of untreated hypertensive patients, at both calcium concentrations, bound significantly less calcium than the control group. Treated and untreated hypertensive individuals had comparable values of membrane calcium binding capacity. Membranes of the treated hypertensive group bound less calcium than those of the normotensive group at both calcium concentrations, but the difference was statistically significant only in the presence of 40 nmol/l free calcium. A significant positive correlation was observed between the calcium binding capacity at 40 nmol/l concentration and that at 1 mumol/l in the treated and untreated hypertensive groups (r = 0.73 and 0.75, respectively; 0.51 for the normotensive group). These findings support the hypothesis that a cell membrane abnormality is detectable in some hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Elevated blood pressure and positive history of kidney stones: results from a population-based study.

Mild hypercalciuria has been observed in hypertension, but it is not yet established whether the prevalence of urinary stone disease is increased as well. Data from the cross-sectional phase of the Gubbio Study--a population-based survey on hypertension involving 5376 subjects (84% response rate)--have been analysed to address this issue, defining as hypertensive those subjects with diastolic pressure falling within the fifth quintile for each sex- and age-specific category, and/or under regular antihypertensive treatment. The prevalence of a positive history for urinary stone (radiographic and/or surgical evidence, and/or stone excretion) was increased by over 50% (P less than 0.01) in treated and untreated hypertensives. None of the 136 subjects with a positive urinary stone history were hypercalcaemic and none had renal failure.

Humans↗
PubMed1988

Development of hypertension after correction of primary hyperparathyroidism.

A statistical association between hypertension and hyperparathyroidism has been repeatedly reported, but the underlying pathogenetic mechanism has not been elucidated. A 51-year-old woman was hospitalized because of increasing motor disability caused by multiple bone and muscle aches with generalized weakness. She was found to have marked hypercalcemia and hypophosphatemia, increased parathyroid hormone secretion, but normal renal function and blood pressure level. After the identification and removal of a single parathyroid adenoma, the calcium/phosphate metabolism normalized in a relatively short time during which, however, hypertension developed in the absence of any other endocrine or renal dysfunction. A positive, highly significant relationship was observed between the progressive rise in blood pressure and the gradual increase in serum phosphate concentration occurring after the operation, suggesting that, in the hyperparathyroid phase, an underlying trend to hypertension could have been masked by the phosphate depletion, probably through its effects on cardiac and vascular smooth muscle function.

Adenoma↗
PubMed1987

Metabolic effects of long-term therapy with muzolimine and chlorthalidone in hypertension.

Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occurred with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested.

Adult↗
PubMed1986

Altered extracellular calcium homoeostasis in essential hypertension: a consequence of abnormal cell calcium handling.

A number of abnormalities in the extracellular and intracellular handling of calcium in arterial hypertension, namely an increased urinary calcium excretion, a reduced serum ionized calcium level and an enhanced intracellular free calcium concentration, have previously been reported by this and other laboratories. The present study aimed to investigate the handling of an exogenous calcium load in hypertensive and normotensive subjects in order to detect possible differences with regard to tissue calcium metabolism in vivo. A constant rate intravenous calcium infusion (0.2 mmol 2 h-1 kg-1 body wt.) was carried out in the participants. Serum calcium concentrations were determined at regular intervals during the infusion and in the 4 h after the end of the calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections. Hypertensive subjects had lower serum ionized calcium levels compared with normotensive subjects at all the experimental points, a finding suggestive of a faster disappearance of calcium from the circulation. The total body calcium clearance, calculated from the area under the curve of the serum calcium concentrations, was enhanced in hypertensive patients (P less than 0.03). Although the renal calcium excretion was higher in hypertension, the renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels achieved by the hypertensive patients were not explained by the renal calcium leak. The enhanced total body calcium clearance found in hypertensive subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of an altered cell calcium handling in hypertension.

Adult↗
PubMed1986

Disturbances of renal and erythrocyte calcium handling in rats of the Milan hypertensive strain.

Urinary calcium (Ca) excretion and erythrocyte membrane Ca binding and transport were investigated in rats of the Milan hypertensive (MHS) and normotensive strains (MNS). Despite slightly reduced ionized Ca levels in the serum, MHS significantly increased urinary Ca excretion under fasting conditions (P less than 0.01). Urinary Ca was positively related to sodium (Na) excretion in both rat strains; moreover the urinary Ca:Na ratio was significantly enhanced in MHS rats (P less than 0.05). These data suggest that in MHS, Ca reabsorption in the renal tubular cell is reduced independently of disturbances in Na handling. Adenosine triphosphate (ATP)-dependent Ca transport, reflecting the Ca, magnesium (Mg)-ATPase activity (Ca pump), was measured in inside-out vesicles obtained from erythrocyte membranes. This variable was significantly reduced in MHS (P less than 0.01), with no change in the Ca pump affinity constant for Ca. Calcium binding to erythrocyte membranes, measured in the presence of free Ca concentrations comparable with those of the intracellular fluid, was found to be significantly reduced (P less than 0.01) in MHS rats because of the lower number of Ca binding sites. These abnormalities of red blood cell (RBC) Ca handling are in keeping with the increased Ca clearance observed in the kidney. It is not clear whether the disturbances of renal and erythrocyte Ca handling were a genetic primary defect or a secondary change of membrane function.

Adenosine Triphosphate↗
PubMed1986

Active Na+ and Ca+ transport, Na+-Ca2+ exchange, and intracellular Na+ and Ca2+ content in young spontaneously hypertensive rats.

The activity of Na+-Ca+-exchange and ATP-dependent Na+ and Ca2+ transport by heart sarcolemmal membranes from male 3-4-week-old spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) were compared. Differences in active Ca2+ and Na+ transport between the two substrains were suppressed by addition of exogenous calmodulin. Calmodulin was active only in the presence of Ca2+. The rate of the Na+-dependent Ca2+ efflux, reflecting the activity of the Na+-Ca2+ exchange, was significantly higher in SHR than in WKY vesicles. An alteration of the intracellular calmodulin activity or content might thus be responsible for the modifications in Ca2+ handling, and limit the activity of the Na+ pump in SHR membranes. The platelet cytosolic free Ca2+ concentration of young SHR and WKY was measured by using the fluorescent indicator Quin-2/AM. In the absence or presence of added external Ca2+, no difference in the intracellular concentration of Ca2+ was observed between platelets of either origin. The intraerythrocytic sodium content, measured by flame spectrophotometry, was similar in SHR and WKY. This study, performed before the onset of hypertension, shows that membrane mechanisms controlling the intracellular ion content were already modified, whereas the resulting intracellular concentrations remained within the normal range.

Animals↗
PubMed1986

Controlled trial of long-term oral calcium supplementation in essential hypertension.

A randomized, double-blind, placebo-controlled crossover trial of oral calcium supplementation was carried out in 18 patients with uncomplicated essential hypertension. After 15 weeks of oral calcium supplementation, 1 g/day, of the patients' habitual diet, the only blood pressure change (compared with the results of placebo treatment) was in the average standing systolic blood pressure, which was significantly reduced (-8.6 mm Hg; p less than 0.01). The 24-hour urinary calcium excretion and the total serum calcium concentration increased significantly during calcium supplementation (p less than 0.05), indicating good compliance with the treatment. The individual blood pressure changes with high calcium intake were found to be inversely related to basal 24-hour urinary calcium excretion (r = -0.69, p less than 0.001 for standing systolic pressure; r = -0.55, p less than 0.002 for standing diastolic pressure). This correlation was independent of age, basal blood pressure, serum calcium concentration, basal 24-hour urinary sodium excretion, and body weight changes during the trial. In particular, a subgroup of six patients, who had a basal 24-hour urinary calcium excretion higher than the mean + 2 SD of a reference healthy population previously described, showed a substantial average blood pressure fall at variance with the other patients in the study. These results do not support the usefulness of an oral calcium supplement in the majority of subjects with mild essential hypertension; however, they suggest that a group of patients with a previously reported abnormality of calcium metabolism may be responsive to this therapeutic measure.

Administration, Oral↗
PubMed1985

The effect of an intravenous calcium load on serum total and ionized calcium in normotensive and hypertensive subjects.

Altered regulation of serum calcium level was proposed to be associated with arterial hypertension and to be dependent on a renal calcium leak or an altered calcium binding to plasma proteins and cell membrane described in human and experimental hypertension. The aim of this study was to analyze the regulation of serum total and ionized calcium levels during an intravenous calcium infusion (0.25 mmol calcium/kg body weight/hr for 2 hours) in a group of untreated essential hypertensives and a comparable normotensive group. Basal serum calcium concentrations did not differ between the two groups, whereas parathyroid activity and urinary calcium were significantly increased in hypertensive subjects. During the calcium load, serum calcium rose almost linearly in all subjects but with a reduced slope in the hypertensive group, which showed serum total and ionized calcium levels significantly lower than those of the controls at the end of the infusion. Our data indicate that hypertensive patients have an altered regulation of serum calcium concentrations, probably due to a different body distribution of calcium, rather than to an altered calcium binding to plasma proteins.

Adult↗