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Biomedical subjects

G Opocher

Publications and source records attributed to G Opocher.

At least 55 records · Page 3Linked to original sources
PubMed1990

Atrial natriuretic peptide infusion in primary aldosteronism. Renal, hemodynamic and hormonal effects.

We have previously shown that a bolus injection of alpha-human atrial natriuretic peptide (alpha-h-ANP) (100 micrograms) in patients with primary aldosteronism induces a transient decrease of blood pressure and a marked natriuresis, but no changes in plasma aldosterone levels. Eight additional cases were studied with a different protocol. Alpha-h-ANP was infused at the dose of 50 ng/kg/min over 1 h, after a bolus of 50 micrograms; saline alone was infused as control. Blood pressure, heart rate, plasma aldosterone, plasma renin activity, cortisol, serum and urinary Na and K and urinary volume were measured. A slight fall in blood pressure, without heart rate changes, was obtained within the first 5 min; this lasted throughout the infusion and for 1 h afterwards. Urinary volume and urinary sodium were significantly higher than controls during the first 2 h, while urinary potassium slightly increased only during the first hour. Plasma renin activity remained suppressed. Plasma aldosterone levels were similar throughout the infusion. Cortisol was not significantly different than placebo except that there was a significant rise after stopping ANP. These data confirm the potent natriuretic effect of ANP infusion and the lack of correlation between ANP induced natriuresis and the effect of ANP on aldosterone in patients with primary aldosteronism.

Adult↗
PubMed1990

New aspects of mineralocorticoid hypertension.

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1990

Role of insulin and atrial natriuretic peptide in sodium retention in insulin-treated IDDM patients during isotonic volume expansion.

Because insulin shows an antinatriuretic effect in healthy humans, insulin therapy resulting in circulating hyperinsulinemia may lead to sodium retention and in turn to hypertension in individuals with insulin-dependent diabetes mellitus (IDDM). Moreover, it has been proved that atrial natriuretic peptide (ANP) plays a major role in modulating natriuresis in humans. This study investigated the relationship between insulin and ANP in modulating sodium metabolism in normotensive and hypertensive IDDM subjects compared with control groups of normotensive and hypertensive nondiabetic subjects. IDDM normotensive and hypertensive subjects had mean +/- SE duration of IDDM of 7 +/- 2 and 8 +/- 2 yr, respectively, and had no clinical features of diabetic nephropathy. All subjects received a saline infusion (2 mmol.kg-1.90 min-1) during euglycemia. IDDM normotensive and hypertensive subjects received a subcutaneous insulin infusion (15 mU.kg-1.h-1), resulting in twofold higher plasma free-insulin levels (16 +/- 2 and 19 +/- 3 microU/ml, respectively) than in nondiabetic normotensive and hypertensive subjects (7 +/- 2 and 8 +/- 2 microU/ml, respectively). During saline challenge, sodium excretion increased by 22 +/- 4% in normotensive and 49 +/- 9% in hypertensive nondiabetic subjects but by only 11 +/- 0.4% in normotensive (P less than 0.01) and 8 +/- 2% in hypertensive (P less than 0.01) IDDM subjects. The impaired natriuretic response to saline challenge was mainly due to greater rates of sodium reabsorption by kidney proximal tubules in IDDM than nondiabetic subjects. At baseline, plasma ANP concentrations were significantly higher in both IDDM groups than in control groups (normotensive IDDM and control subjects: 38 +/- 4 and 19 +/- 2 pg/ml, respectively, P less than 0.01; hypertensive IDDM and control subjects: 45 +/- 6 and 27 +/- 4 pg/ml, respectively, P less than 0.05). After saline challenge, ANP concentrations rose to 39 +/- 4 pg/ml in normotensive and 49 +/- 5 pg/ml in hypertensive control subjects, whereas no significant change above baseline value was seen in IDDM subjects. Both IDDM groups showed a 10-12% greater exchangeable Na+ pool than control subjects regardless of the presence of hypertension. Subcutaneous insulin infusion, resulting in circulating plasma free-insulin levels in normotensive control subjects comparable to those in IDDM patients, inhibited natriuresis, increased proximal tubule sodium reabsorption at the level of the kidney, and inhibited an adequate ANP stimulation by saline challenge. We conclude that hyperinsulinemia leads to increased proximal tubule sodium reabsorption and impaired ANP response during saline administration. Both mechanisms account for sodium retention in normotensive and hypertensive IDDM patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Lack of aldosterone inhibition by atrial natriuretic factor in primary aldosteronism: in vitro studies.

Several studies demonstrated that aldosterone secretion, by bovine, rat and human glomerulosa cells, is inhibited in vitro by atrial natriuretic factor (ANF). This effect has also been investigated with conflicting results in cells taken from aldosterone-producing tumors. In the present study, atrial natriuretic factor has been tested on aldosteronoma cells obtained from 4 patients with primary aldosteronism. The cells were studied both with perfusion and incubation systems. Aldosterone secretion was stimulated by ACTH, angiotensin II and potassium with or without ANF 10 microM. In this study ANF lacked to inhibit either basal and stimulated aldosterone secretion, indicating some alterations of ANF-adrenal interaction in this syndrome.

Adenoma↗
PubMed1989

Atrial natriuretic factor in hypertensive and normotensive insulin-dependent diabetics.

Since insulin increases renal sodium reabsorption, hyperinsulinaemia in insulin-treated insulin-dependent diabetes mellitus might lead to sodium retention and, in turn, increase atrial natriuretic factor (ANF) values. We investigated ANF levels in insulin-dependent diabetes mellitus with and without hypertension. We infused saline (2 mmol/kg per 90 min) in nine normotensive controls, eight normotensive diabetics, seven hypertensive controls and six hypertensive diabetics during the imposition of a euglycaemic glucose clamp with an artificial pancreas. Baseline ANF values were higher in the normotensive and hypertensive diabetics than in the normotensive and hypertensive controls. During a sodium load the sodium excretion rate increased significantly in controls but not in the diabetic groups. The ANF pattern was similar, values being significantly increased in controls and unchanged in diabetic patients. We conclude that euglycaemic, slightly hyperinsulinaemic, insulin-dependent diabetes mellitus patients with and without hypertension are characterized by higher baseline ANF values and an impaired response to an acute saline load as shown by the sodium excretion rate and the plasma ANF concentration.

Atrial Natriuretic Factor↗
PubMed1989

Acute and chronic effect of nifedipine in primary aldosteronism.

Since calcium entry blocker drugs can interfere with aldosterone secretion in vitro, a similar effect in vivo, in man, has been suggested and partially confirmed. The data available in primary aldosteronism are more controversial. Therefore, we have studied the acute and chronic effect of nifedipine in 7 patients with idiopathic hyperaldosteronism (IHA) and 8 with aldosterone producing adenoma (APA). On 2 different days, 10 mg of nifedipine or placebo were given sublingually to the patients and blood pressure and heart rate were recorded every 5 min. for 60 min. Plasma aldosterone, cortisol, PRA and serum K+ were measured at 0, 30 and 60 min. 5 patients with IHA and 6 with APA received nifedipine 20 mg per os bid for 3 months; the same parameters were evaluated on days 0, 30, 60 and 90; urinary aldosterone was measured on days 0, 30, 60 and 90. BP decreased in both groups both after acute and chronic administration of nifedipine. Plasma aldosterone showed a similar trend either after acute nifedipine or placebo; however, during chronic treatment it was slightly decreased in IHA patients. Cortisol, PRA, urinary aldosterone and K+ remained unchanged. In conclusion, nifedipine is an effective antihypertensive agent also in primary aldosteronism; its aldosterone inhibiting properties are minimal and seem to be present only during long-term therapy in IHA.

Adenoma↗
PubMed1987

Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma.

In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.

Adolescent↗
PubMed1987

Effect of verapamil on aldosterone secretion in primary aldosteronism.

Intracytoplasmic calcium seems to act as second messenger for aldosterone secretion. Both in vitro and in vivo studies demonstrate that drugs which block calcium entry cause a decreased responsiveness of glomerulosa cells to Angiotensin II and potassium. In order to evaluate the effect of a calcium channel blocking agent (Verapamil) in conditions of abnormal aldosterone secretion, we have studied 11 patients with primary aldosteronism, 5 with idiopathic hyperaldosteronism (IHA) and 6 with aldosterone producing adenoma (APA). In our study plasma aldosterone levels decreased after Verapamil infusion in IHA whereas no significant variations were observed in APA patients. These results suggest that calcium blockade can interfere with a possible regulatory system which plays a greater role in idiopathic aldosteronism.

Aldosterone↗
PubMed1986

Effect of verapamil on the aldosterone-stimulating properties of metoclopramide: in vitro and in vivo studies.

The role of calcium in the regulation of aldosterone secretion has been recently clarified. Angiotensin II and potassium stimulate aldosterone secretion through a calcium-entry dependent mechanism, while ACTH action is both calcium and cyclic AMP dependent. To establish whether also the so-called aldosterone dopaminergic regulatory system is calcium-dependent we have studied, in vitro and in vivo, the effect of verapamil, a calcium entry blocker agent, on the aldosterone-stimulating properties of the antidopaminergic drug, metoclopramide. In the rat adrenal cells perfusion system, verapamil blocked both angiotensin II and metoclopramide-stimulated aldosterone. This effect on metoclopramide action seems to be present also in vivo in normal subjects: in fact aldosterone response was slightly but significantly reduced after pretreatment with verapamil. In conclusion the results suggest that also the dopaminergic system could regulate aldosterone secretion through calcium-mediated mechanisms.

Adrenal Glands↗
PubMed1986

Opioid modulation of normal and pathological human chromaffin tissue.

To evaluate whether opioid receptor blockade might modulate sympathetic-adrenal activity, we studied the effects of placebo or naloxone administration on plasma catecholamine (CA) levels in a group of 13 normal subjects and 15 hypertensive patients suspected to have a pheochromocytoma. Diagnostic evaluation confirmed the presence of pheochromocytoma in 9 patients. Among these, 4 had a unilateral epinephrine (E)-secreting tumor, 3 had bilateral E-secreting tumors due to multiple endocrine adenomatosis type IIa, and 2 had a unilateral norepinephrine (NE)-secreting tumor. In each subject studied, CA secretion was evaluated by calculating the area (0-30 min) under the plasma hormone curves after placebo or naloxone administration. In normal subjects naloxone caused a significant increase (P less than 0.005) of E secretion, whereas NE did not change. Similarly, in the group of hypertensive patients, E secretion increased after naloxone (P less than 0.01). In pheochromocytoma patients naloxone caused a significant increase in E (P less than 0.05) and NE (P less than 0.01) secretion from E-producing tumors but no increase in the patients with NE-secreting pheochromocytomas. The study suggests that CA secretion from normal and pathological chromaffin tissue is modulated by endogenous opioids; this modulation seems particularly evident in patients with E-secreting pheochromocytoma.

Adolescent↗
PubMed1986

Renin-angiotensin-aldosterone system: a long-term follow-up study in 17 alpha-hydroxylase deficiency syndrome (17OHDS).

We studied the mineralocorticoid pattern in 4 patients with 17OHD during long-term glucocorticoid treatment. We observed reduction of BP, normalization of K levels, a gradual increase in PRA and in urinary Aldosterone (ALDO); a normal response of plasma ALDO to ACTH and to angiotensin II was present only in one case. We observed a prompt decrease of mineralocorticoid hormones, normalized by long-term therapy only in one case. Discontinuation of treatment induced an increase of ALDO that became suppressed in late off-treatment. Thus, glucocorticoid treatment decreases abnormal steroid levels and activates zona glomerulosa (ZG) function, even if it may take years for ALDO to normalize. Brief discontinuation of therapy induces a surge in ALDO levels, revealing no biosynthetic defect in ZG, while in late off-treatment mineralocorticoids seem to come exclusively from zona fasciculata.

Adolescent↗
PubMed1986

Effect of ketanserin on the in vitro regulation of aldosterone.

Serotonin (5-HT) is known to be a potent stimulator of aldosterone release in vitro and, to a lesser degree, in vivo. Since ketanserin, a specific 5-HT2-receptor antagonist, decreases aldosterone levels in some hypertensive patients, we have performed in vitro experiments to elucidate the mechanism by which ketanserin interferes with aldosterone regulation. After collagenase dispersion, rat zona glomerulosa cells were either perfused and resuspended in Biogel or incubated in Earle's medium and bovine serum albumin. The cells were stimulated with serotonin, angiotensin II, potassium (K+) and adrenocorticotrophic hormone (ACTH) in the presence or absence of ketanserin. Ketanserin did not decrease baseline aldosterone secretion although it reduced the stimulatory capacity of serotonin and K+, and had a minimal effect on ACTH. Furthermore, we demonstrated that ketanserin is able to have a significant effect on the adrenal response to angiotensin II. These data indicate that antiserotoninergic agents may act directly at the level of the adrenal glomerulosa by interfering with specific serotoninergic receptors and modifying the adrenal sensitivity to angiotensin II and K+. The importance of these findings in the clinical use of these antihypertensive drugs remains to be established.

Adrenocorticotropic Hormone↗
PubMed1985

Effect of ketanserin in primary aldosteronism.

Serotonin is known to have aldosterone-stimulating properties in humans, which are counteracted by the serotonin-antagonist metergoline. Suppression of aldosterone levels by cyproheptadine in patients with idiopathic aldosteronism has also been shown. Since ketanserin, a more specific 5-HT2-serotoninergic (5-HT2) antagonist, has been shown to affect aldosterone secretion in essential hypertension, we have further investigated this mechanism by injecting ketanserin (10 mg i.v.) in 10 patients with primary aldosteronism (four adenoma, six idiopathic aldosteronism). A transient decrease (20% when compared with the basal levels) of plasma aldosterone was seen at 30 min. A concomitant decrease of plasma cortisol was also noticed, whereas plasma renin activity and potassium did not change. Blood pressure decreased in all cases. These observations suggest that ketanserin acts directly at the adrenal level by interfering with a possible modulatory activity of serotonin. However, an adrenocorticotropic hormone-mediated effect cannot be completely ruled out at the present time.

Aldosterone↗
PubMed1983

Effect of metergoline on the aldosterone-stimulating properties of metoclopramide.

The mechanism by which metoclopramide stimulates aldosterone secretion is still unclear, since it cannot be explained by known regulatory systems. On the other hand we have recently shown that serotonin is also a potent aldosterone-stimulatory substance in man and its action can be blunted by the antiserotoninergic drug, metergoline. To test if metoclopramide could act through a serotoninergic pathway we have studied the effect of metergoline on the aldosterone response to metoclopramide in 8 normal subjects. The effect of metoclopramide (10 mg i.v.) on plasma aldosterone, PRA, cortisol, prolactin and K was studied before and after acute metergoline administration. Metergoline pretreatment significantly reduced the aldosterone response to metoclopramide, together with a slight reduction of prolactin, whereas no changes were seen on PRA, cortisol and K. In vitro, metoclopramide induced a significant aldosterone output from human adrenal adenoma cells, which was partially reduced by metergoline and not by bromocriptine. Despite a lack of specificity of metergoline these data may suggest the hypothesis of a serotoninergic component in the aldosterone-stimulating properties of metoclopramide.

Adenoma↗
PubMed1983

Insulin resistance in Cushing's syndrome.

It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood. We studied five women with Cushing's syndrome with impaired oral glucose tolerance tests and seven normal subjects, plotting the shape of the insulin-induced disposal dose-response curve obtained by means of the euglycemic clamp procedure during four different plasma insulin plateaus at four infusion rates of 21, 73, 760, and 1200 mU/M2 . min. Glucose disposal (M = mg/M2 . min) was calculated as glucose amount infused to maintain euglycemia. In Cushing's syndrome the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M (337 +/- 35 vs. 657 +/- 76 P less than 0.01) during the highest insulin infusion rate [maximal glucose disposal (MGD)] without any significant difference in the levels of insulin half-maximally effective in the stimulation of glucose utilization. Neither erythrocyte nor monocyte maximum insulin receptor binding were different between the two populations. Four Cushing's syndrome patients were studied again after surgical treatment. A marked improvement of MGD was observed without any significant change in insulin-binding capacity. These results, particularly the marked decrease in MGD, a typical feature of postreceptor defects, indicate that cortisol-induced insulin resistance in man is due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step.

Adult↗
PubMed1982

Peripheral and renal vein plasma renin activity in hypertensive urological patients.

Upright plasma renin activity (PRA) was measured in 112 patients suffering from urological diseases associated with hypertension, and was found to be predominantly low. In 40 cases with normal or elevated peripheral PRA, renal venous PRA was measured and their ratios calculated. There was a significant decrease of blood pressure in 14 patients who had undergone surgery and both ratios were significant. The patients whose blood pressure remained unchanged had no significant renal vein PRA ratios. However, one case with nonlateralising renal venous PRA ratios responded well to surgery. It is concluded that although peripheral vein PRA is of limited value in hypertension associated with urological diseases, the measurement of PRA in renal vein plasma offers, in a number of cases, useful prognostic information.

Adult↗