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S Rocco

Publications and source records attributed to S Rocco.

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

Interaction between serotonin and other regulators of aldosterone secretion in rat adrenal glomerulosa cells.

Although serotonin (5HT) is a recognized stimulator of aldosterone secretion in vivo and in vitro, its physiological role as a regulator of mineralocorticoid secretion and its mechanism of action in the adrenal glomerulosa have not been elucidated. To address these questions we studied the interaction of 5HT with other aldosterone regulators in isolated rat adrenal glomerulosa cells. 5HT stimulated aldosterone production 14-fold, with an ED50 of 20 +/- 5 nM, and stimulation was maximal at 0.8 microM. The stimulation of aldosterone production by 5HT was accompanied by a 5-fold increase in cAMP production, with an ED50 of 1 microM. Threshold levels of 5HT (1 nM) potentiated the effect of submaximal concentrations of angiotensin-II (AII), decreasing the ED50 from 1.3 to 0.46 nM and increasing the maximum response in an additive manner. In contrast, the stimulatory effect of 5HT was purely additive to that of submaximal ACTH concentrations. 5HT had no effect on aldosterone secretion stimulated by maximal ACTH concentrations, despite full additivity on cAMP accumulation. Stimulations of steroidogenesis by potassium and 5HT were fully additive at submaximal concentrations, but only partially additive at-maximal levels. To determine the mechanism of the synergistic effects of AII and 5HT, we analyzed the interaction of both stimuli on cAMP accumulation, intracellular calcium, and inositol phosphate formation. Consistent with the inhibitory effect of AII on adenylate cyclase, in the presence of AII the stimulation of cAMP by 5HT was reduced by 18 +/- 3%. 5HT alone had no effect on cytosolic calcium, but significantly enhanced the peak and later phases of the AII-stimulated increase (P less than 0.005). This effect of 5HT was due to calcium influx and not to release from intracellular pools, as shown by suppression of the potentiation in the absence of extracellular calcium and the lack of effect of 5HT on basal or AII-stimulated inositol phosphate formation. The ability of low concentrations of 5HT to potentiate the stimulatory effect of AII on aldosterone secretion suggests that under some physiological conditions, 5HT may play a role in regulating the adrenal sensitivity to AII.

Adrenocorticotropic Hormone↗
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

Aldosterone and pressor responses to angiotensin II in primary hyperparathyroidism.

The aim of this study was to assess the effect of hypercalcaemia due to primary hyperparathyroidism on the pressor and aldosterone responses to angiotensin II (Ang II) infusion. Five patients with hyperparathyroidism were studied, before and after parathyroidectomy, and were compared with five normal subjects. After 30 min of equilibration, Asp1-Val5 Ang II was infused in all subjects at stepwise increasing dose rates of 2 and 4 ng/kg per min for 30 min each. In the hyperparathyroid patients the baseline levels of plasma parathyroid hormone and calcium were significantly higher than in the controls, and returned to normal after the parathyroidectomy; plasma aldosterone and renin activity were normal both before and after the parathyroidectomy. Two hyperparathyroid patients had high blood pressure levels, which were normalized after surgery. The increase in the aldosterone response from baseline at each time point of the Ang II infusion was greater in the hyperparathyroid patients before than after the operation (P less than 0.05), and greater than in the normals (P less than 0.05). No difference in the increased response of systolic or diastolic blood pressure was observed between the hyperparathyroid patients, either before or after the parathyroidectomy, and the normal subjects. High levels of extracellular calcium or parathyroid hormone, or both, might play a primary role in the aldosterone hyper-responsiveness to Ang II in the hyperparathyroid patients. The similar pressor response to Ang II in hyperparathyroid patients and the normal subjects suggests that hypercalcaemia does not potentiate the vasoconstrictive action of Ang II.

Adult↗
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↗
PubMed1988

An ultrastructural stereologic study of aldosterone secreting adrenal adenomas and of adjacent zona glomerulosa.

The ultrastructure of four aldosterone secreting adenomas and of the adjacent zona glomerulosa has been described by the use of stereological techniques. Adenomatous cells (about 2800 microns 3 in volume) invariably displayed a striking abundance of lipid droplets, which occupied about 30% of the cytoplasm. Mitochondria prevalently contained tubulo-lamellar or lamellar cristae, but some cells exhibited organelles with vesicular cristae. Smooth endoplasmic reticulum (SER) was not very abundant. Small lipofuscin-pigment granules were frequently seen and in a few cells they were exceedingly numerous. Zona glomerulosa cells were smaller (about 950 microns 3 in volume) and possessed mitochondria with typical tubulo-lamellar cristae, a plentiful SER and few lipid droplets. They showed the ultrastructural features of elements actively engaged in steroid synthesis. The possible origin of aldosteronoma cells from the zona glomerulosa is discussed.

Adenoma↗
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↗
PubMed1987

Alpha-h-ANP injection in normals, low renin hypertension and primary aldosteronism.

Atrial natriuretic peptide, a hormone secreted by the heart, is involved in salt and fluid homeostasis and also exerts an inhibitory effect on aldosterone production in vitro. In order to elucidate if this effect is also present in man, 6 normal volunteers, 5 low renin hypertensive patients (LRH) and 7 patients with primary aldosteronism (PA) have received 100 micrograms of alpha-h-Anp as bolus i.v. (The decrease in blood pressure was mild and transient in all groups, whereas a marked diuretic effect was observed in all hypertensives even in PA where high levels of endogenous ANP have been found. In normals we observed a significant decrease of plasma aldosterone values while in PA and LRH this effect was not evident. This phenomenon associated with a greater natriuretic effect in LRH and PA, as compared with normals, demonstrates the lack of the correlation between ANP-induced diuresis and aldosterone inhibiting properties.

Adult↗
PubMed1987

Effect of alpha-human atrial natriuretic peptide in low renin essential hypertension and primary aldosteronism.

Atrial natriuretic peptide (ANP), besides its diuretic and antihypertensive effects, exhibits an "in vitro" inhibitory action on aldosterone. In order to elucidate if these effects are present also "in vivo", we injected 100 micrograms of alpha-human ANP as a bolus in normal volunteers, low renin essential hypertensive subjects (LRH) and in patients with primary aldosteronism (PA). A transient hypotensive effect was seen in all patients, without significant variations of heart rate. The diuretic and saluretic effects of ANP were greater in hypertensive subjects, even in PA where endogenous ANP levels are known to be elevated. Plasma aldosterone values decreased significantly only in normal volunteers. In conclusion, in LRH and PA renal effects of ANP are not diminished, although its aldosterone-inhibiting properties are less evident than in normals.

Adolescent↗
PubMed1987

Ketanserin versus nifedipine in the treatment of essential hypertension in patients over 50 years old: an international multicenter study.

The serotonergic antagonist ketanserin (K) was compared to nifedipine (N) in a five-center international study on hypertensive patients over the age of 50 years. After a 4-week placebo run-in period, patients were randomly assigned to receive for 3 months either ketanserin (40 mg b.i.d. after 2 weeks of 20 mg b.i.d.) or nifedipine (20 mg N retard b.i.d.). After 1 month, monotherapy patients whose blood pressure was not sufficiently reduced received a diuretic in combination therapy. At the end of the active treatment period, patients who had remained on monotherapy received placebo until hypertension returned or for a maximum of 2 months. One hundred and seventeen patients were entered in the study, 58 on K and 59 on N. More patients switched to combination with a diuretic in the K group (14 patients) than in the N group (6 patients). The overall reduction in blood pressure was similar for K and N. Total response rate was high (96%) for the two drugs. Blood pressure was reduced both at peak and trough drug levels. No orthostatic reactions were observed, and no rebound hypertension occurred at discontinuation of therapy. Ketanserin monotherapy slightly decreased heart rate (-1 beats/min). whereas N produced a significant increase (+6 beats/min). Body weight significantly increased with K (+1.1 kg) and was unchanged with N. More patients complained of adverse reactions during N monotherapy (47%) than during K monotherapy (34%). Flushing and leg edema were more frequent with N.

Blood Pressure↗
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

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

The risk of hepatitis A virus infection for hospital staff.

The prevalence of antiHA was assessed in 594 hospital employees and in control groups comprising 932 "healthy" adults not working in the hospital, selected from different socioeconomic classes. Age specific antiHA prevalence which was lower in doctors than in nurses and ancillary staff, was also found to be lower in each group than in the respective controls, matched according to socioeconomic criteria. It is concluded that in our population (i.e. high risk area) the hospital environment does not involve an increased risk of HAV infection for personnel. However, precautions should be taken when working in high risk department, as this study demonstrated that a considerable proportion of health care workers (above all doctors) are still susceptible to Hepatitis A virus infection.

Hepatitis A↗