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Biomedical subjects

D Cusi

Publications and source records attributed to D Cusi.

At least 73 records · Page 4Linked to original sources
PubMed1986

A renal abnormality in the Milan hypertensive strain of rats and in humans predisposed to essential hypertension.

Many similarities in kidney-function abnormalities were found between hypertensive rats of the Milan strain (MHS) and young normotensive human subjects with hypertensive parents, compared with the appropriate controls. These similarities included an increased glomerular filtration rate, increased pressor effect of the kidney after transplantation, increased 24-h urinary output and lower plasma renin activity and urinary kallikrein. The isolated MHS kidney perfused in vitro with an artificial medium had a higher glomerular filtration rate, a higher urinary output, higher tubular sodium reabsorption and higher oxygen consumption than the kidney of control Milan normotensive rats (MNS). Further, reogenic sodium transport across brush border vesicles isolated from proximal tubular cells is faster in MHS than in MNS. Erythrocytes and proximal tubular cells of MHS have a lower volume and sodium content than those of MNS, while sodium transport is faster and the Ca2+-ATPase at Vmax is lower. This indicates that the 'genetic' cellular abnormality responsible for the renal-function abnormality and the hypertension is also present in erythrocytes. Thus these cells may be used to study the genetic cellular mechanisms of hypertension. Experiments with bone marrow transplantation and with F2 hybrids obtained by crossing the F1 (MHS X MNS) hybrids showed that the MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with the hypertension. Since, in human hypertensives, there was a correlation between abnormal erythrocyte sodium transport and renal function, it is proposed that erythrocytes may be used in studying the cellular molecular mechanisms of hypertension.

Animals↗
PubMed1984

Genetic hypertension and the kidney.

The relationship between the kidney and genetic hypertension has been assessed in light of the changes seen in some kidney and cell functions during the phases preceding and accompanying the development of "genetic" types of hypertension in rats and humans. Comparison of the kidney function of normotensive subjects likely to develop hypertension with that of matched controls resistant to hypertension showed, in the former, a higher glomerular filtration rate (GFR), greater tubular reabsorption, larger 24-h urinary output, larger fraction of cardiac output to the kidney, and lower plasma renin activity. After the transplantation of a kidney from a subject in the hypertension-prone group, recipients had higher blood pressure and required more antihypertensive therapy than recipients of kidneys from the hypertension-resistant group. In humans this finding is not as clear as in rats. During the development of hypertension most of these differences in kidney function in the two groups of subjects tend to disappear. The changes in cell function, measured particularly in rats, were consistent with the organ function changes. Cell volume and sodium content were lower, while the transport rate across the cell membrane was faster in proximal tubular cells of rats with genetic hypertension than in the appropriate controls. This is in keeping with the concept of a primary increase in proximal tubular reabsorption leading, on the one hand, to an increase in GFR and renal blood flow and a decrease in renin and, on the other, to an increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sodium balance and peripheral resistance in arterial hypertension.

In this brief review, some aspects of the relation between sodium balance and peripheral resistance in four types of arterial hypertension are discussed. Renal hypertension, hypertension caused by reduced kidney mass and sodium load, mineralocorticoid hypertension, and spontaneous or "genetic" hypertension in rats are considered. In all these forms of hypertension, the increase in peripheral resistance is preceded by changes in body sodium and fluids. However, the precise role of these changes in the development of the subsequent rise of peripheral resistance is not yet clear. Changes in ion transport across the cell membranes have been demonstrated even before the development of hypertension, especially the forms caused by mineralocorticoids or genetic factors. Even though we do not know the underlying mechanisms, it is very likely that these cell-membrane changes are involved in the rise of peripheral resistance and blood pressure.

Animals↗
PubMed1983

Renal dysfunction as a possible cause of essential hypertension in predisposed subjects.

In 65 young normotensive subjects with two hypertensive parents (HP), and in 55 matched subjects with two normotensive parents (NP), the following factors were measured: renal plasma flow (RPF), glomerular filtration rate (GFR) both as Inutest and creatinine clearances; 24-hr urinary output; plasma renin activity (PRA); Na and K in plasma and in 24-hr urine and 24-hr urinary excretion of aldosterone. In 30 HP and in 34 NP, the cardiac output and plasma concentrations of noradrenaline, adrenaline, and dopamine were also measured in the supine position and after 10 min of standing. The HP have greater RPF (P less than 0.01), faster GFR (P less than 0.02), greater 24-hr urinary output (P less than 0.05), and lower PRA (P less than 0.01) than the NP. All the other factors were similar in the two groups of patients. It is proposed that the differences in renal function in the HP and the NP may be due to an abnormality in tubular handling of ions and water in the HP, which may be responsible for the increase in blood pressure in a proportion of patients with essential hypertension.

Adolescent↗
PubMed1982

Active and inactive renin and kidney function in young subjects with different predisposition to develop essential hypertension.

Renal and cardiac function were measured in 65 offspring of hypertensive parents (OHP) and in 56 offspring of normotensive parents (ONP). In two additional groups of 24 OHP and 42 ONP plasma renin activity (PRA) and plasma active (PRAC), inactive (PRIC) and total (PRTC) concentration were measured. OHP had significantly higher renal plasma flow (p less than 0.01), glomerular filtration rate (p less than 0.02) and 24-hour urinary output than ONP, while PRA was lower (p less than 0.01). The measurements of the different forms of renin gave the following results: PRIC and PRTC were lower in OHP than in ONP, but the only statistically significant difference concerns PRIC (p less than 0.025). A possible interpretation of these findings is that a primary increased tubular ion and water reabsorption might be the cause of the kidney function pattern seen in OHP.

Catecholamines↗
PubMed1981

Relationship between altered Na+--K+ cotransport and Na+--Li+ countertransport in the erythrocytes of 'essential' hypertensive patients.

1. The maximal rate of activity of sodium extrusion by the sodium pump, Na+--K+ outward cotransport, passive permeability to sodium and potassium, Na+--Li+ countertransport, and passive permeability to lithium were measured in 45 essential hypertensive patients, 24 young normotensive subjects with at least one hypertensive parent and 24 normotensive subjects with both parents normotensive. 2. The maximal rate of activity of the sodium pump and the rate constants for passive permeability to sodium, potassium and lithium were similar in the three groups. 3. The mean value for Na+--K+ outward cotransport was significantly lower and that for Na+--Li+ countertransport significantly higher in the hypertensive patients than in the normotensive subjects without a family history of hypertension, but there was a great overlap between individual values. The offspring of hypertensive parents had intermediate values. 4. A highly significant positive correlation existed between Na+--K+ cotransport and Na+--Li+ countertransport both in the normotensive and in the hypertensive subjects, indicating that in the latter there were some with high Na+--Li+ countertransport and others with low Na+--K+ cotransport. 5. In nine hypertensive families studied, if an alteration of the transport system was detected in a hypertensive propositus, the same type of alteration was also found in his still normotensive offspring, thus indicating a familial tendency for the alteration to occur.

Adolescent↗
PubMed1981

Familial aggregation of cation transport abnormalities and essential hypertension.

The maximal rate of activity of Na extrusion by the Na pump, Na-K outward cotransport, Na-Li countertransport and the rate constant for passive permeability to Na, K and Li were measured in the RBC of 24 normotensive subjects with both parents normotensive, 45 hypertensive subjects and 24 of their normotensive offspring. The Na extrusion by the Na pump and the passive permeability to Na, K and Li are equal. The hypertensives have significantly greater Na-Li countertransport and smaller Na-K cotransport when compared to the normotensives. Na-K cotransport and Na-Li countertransport are positively correlated, thus suggesting some relationship between the two systems. When arbitrary normal limits are set the hypertensives are divided in three groups: normal cotransport and countertransport (22.2%) high countertransport (31.1%) and low cotransport (44.4%). In nine hypertensive families studied if either alteration was observed in a hypertensive propositus, this was of the same kind as the one in case observed in any first degree relative, whether already hypertensive or young normotensive. The observed alterations are primitive to the development of hypertension and possibly related to its pathogenesis.

Adolescent↗
PubMed1979

A renal abnormality as a possible cause of "essential" hypertension.

The renal abnormality which causes hypertension in the Milan hypertensive strain of rats disappears as hypertension develops. Because of the many analogies between the condition in these rats and "essential" hypertension in man, the same pattern of change may occur if a renal abnormality is the cause of essential hypertension in man. This hypothesis was tested in two groups of young normotensive subjects matched for age, sex, and body-surface area; in the first group both parents were hypertensive, and in the second group both parents were normotensive. Renal plasma-flow, glomerular filtration-rate, plasma-volume, plasma-renin activity, plasma-concentrations of Na+, K+, and catecholamines, 24 h urinary excretion of Na+, K+, and aldosterone, and the cardiac index were measured so that renal function and the role of factors affecting blood-pressure regulation could be assessed. Renal plasma-flow was significantly higher (p less than 0.01) in the first group, whereas results of tests for all the other factors were almost the same in both groups. The hypothesis that a primary kidney abnormality causes hypertension in a proportion of patients with essential hypertension is proposed.

Adult↗
PubMedDate not supplied

[Genetic basis for malformation-associated uropathy and renal dysplasia].

The wide association between urinary tract malformations and dysplastic kidneys, known as CAKUT (Congenital Anomalies of the Kidney and Urinary Tract), could be caused by a single disorder of the embryonic development of the kidney and urinary tract. These complex patterns of development are under genetic control. A positive family history strongly suggests a genetic origin of these conditions. Linkage studies show an extreme genetic heterogenicity and an important phenotypic and clinical variability of the same mutation. Some urinary tract malformations have been investigated in the context of clinical syndromes. The renal-coloboma syndrome is an autosomal dominant human disease, secondary to mutation of the PAX2 transcription factor, characterized by optic nerve coloboma, renal anomalies and vesicoureteral reflux. However, most of the urinary tract anomalies can occur in isolation. Studies have shown the association of hereditary hydronephrosis with HLA antigens on chromosome 6 and the association of VUR with the mutations in a locus of chromosome 1. The higher frequency and severity of some uropathies in the male gender may be explained by a linkage-disequilibrium phenomenon or a X-linked transmission pattern. For example, the mutations in the AGTR2 gene on chromosome X were observed in animal models but not yet confirmed in human subjects. Finally, the ACE gene polymorphism is associated with a higher incidence of congenital hypo-dysplastic kidneys and represents a significant risk factor for the development of progressive renal damage.

Abnormalities, Multiple↗
PubMedDate not supplied

[Pregnancy during nephropathy].

We illustrate two cases of pregnancy complicated by previously onset chronic nephropathy. In spite of two completely different pathogenetic mechanisms for chronic renal insufficiency (IgA nephropathy in one case and vescico-ureteral reflux in the other), renal function at the beginning of the pregnancy was similar and only partially impaired. In either case the pregnancy lowered by 50% the residual glomerular filtration rate. Only minimum recovery was observed during several months of follow-up.

Adult↗
PubMedDate not supplied

[Genetics and arterial hypertension: monogenic forms].

Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. The study of genes involved in rare forms of monogenic hypertension led to the identification of pivotal pathophysiological pathways of kidney sodium and water reabsorption that can influence blood pressure values when changed. Glucocorticoid-Remediable Aldosteronism (GRA) is characterised by normal to high aldosterone levels, despite plasma renin activity suppression, and by the fact that these alterations are corrected by exogenous glucocorticoid administration. Apparent Mineralocorticoid Excess (AME) is due to a mutation of the gene encoding the renal isoform of 11 â HSD enzyme; the non-conversion of cortisol to cortisone result in increasing cortisol levels that activate the mineralocorticoid receptor. Early onset hypertension exacerbating during pregnancy is caused by a mutation leading to a conformational change in the mineralocorticoid receptor. Therefore, substances that are normally inactive at this level, such as progesterone, become potent agonists of the mutated receptor. Liddle's syndrome (or type I pseudo-hyperaldosteronism (PHA1), is characterised by a constitutive activation of the epithelial sodium channels in the distal tubule, causing an increase in sodium and chloride reabsorption. Gordon syndrome (Type II pseudo-hyperaldosteronism, PHA2) differs from the other forms because of the presence, in addition to hypertension, of hyperkaliemia and hyperchloremic acidosis that can be normalized with thiazide diuretics. Finally, a large pedigree of Turkish origin has been described: these patients are affected by an uncertain form of monogenic hypertension associated with brachydactyly.

Glucocorticoids↗
PubMedDate not supplied

[Renal tubular transport and genetic hypotension].

The progressive improvement of genetic research technologies has led to the identification of different genes involved in blood pressure regulation. Renal regulation systems of sodium homeostasis play a key role. Mutations capable of determining an increase or a decrease in carrier proteins function could cause not only hypotension or hypertension, but also the related metabolic symptoms and changes, and the possible response to pharmacologic treatment. Monogenic forms of hyper- or hypotension are rare, though they highlight the importance of sodium tubular transport in blood pressure adjustment.

Homeostasis↗
PubMedDate not supplied

[Cellular metabolism of sodium and hypertension].

Essential hypertension develops from interactions between genetic and environmental components. Studies on cell membrane ions (in particular the sodium ion) transport in essential hypertension were originally carried out in order to better understand the roles these two components play in a less complex system than the overall organ system or the single organs involved in blood pressure regulation. The theory supporting this experimental approach is based on the observation that cell membrane function affects all the phenomena involved in blood pressure regulation. Receptor function, hormonal secretion, cell volume regulation, ion transport and ion composition of the cell are all regulated at the cell membrane level. However the problem of the relevance of cellular sodium metabolism in the pathogenesis of essential hypertension and of the interpretation of the many conflicting results has grown in complexity with the growing mass of data published in the literature. At least part of this complexity seems related to methodological problems but part is surely due to real differences among the various populations or subpopulations studied. This review analyzes the main sources of the discrepancies, the different ion transport systems and the end point of the overall transport system as well as the steady state intracellular cation concentration in both genetic animal models of essential hypertension and in man.

Animals↗