Ethnicity-related variations of left ventricular remodeling in adolescent amateur football players.

Adult and adolescent elite black athletes display - as compared with their white counterparts - excessively increased left ventricle (LV) wall thickness (LVWT), mass (LVM), and relative wall thickness (RWT). To investigate such ethnicity-related differences in non-professional adolescent athletes, 138 male, amateur football players [age 14.0 ± 1.7 years, 42 West-African blacks (BA) and 96 Italian whites (WA)] underwent an echocardiographic study of LV diameters, LVWT, maximal wall thickness (MWT), LVM, and RWT as remodeling index. BA vs WA exhibited greater thickness of septum and posterior wall, higher MWT (10.3 ± 1.7 vs 8.8 ± 1.1 mm), and higher LVM (117 ± 27 vs 101 ± 20 g/m(2)) and RWT (0.44 ± 0.07 vs 0.35 ± 0.04). Age, systolic blood pressure, body mass index, and ethnicity predicted MWT and LVM, whereas ethnicity was the sole strong predictor of RWT. The greater MWT, LVWT, and LVM of 14-year-old, amateur-level BA vs WA indicates that ethnicity substantially affects LV structure in adolescent, non-professional athletes. In contrast with MWT and LVM, elevated RWT was predicted by black ethnicity only. We suggest that concentric-type LV remodeling is a peculiar LV phenotype in adolescent African athletes.

Early abnormalities in left ventricular diastolic function of sodium-sensitive hypertensive patients.

The aim of this study was to evaluate whether salt-sensitivity in essential hypertension produces a significant comparative difference in diastolic function and ventricular mass when compared with sodium-resistance. Recent epidemiological data have demonstrated a positive correlation between sodium intake and arterial pressure. Furthermore, a positive correlation has been detected between sodium intake and left ventricular hypertrophy (LVH) independently of arterial pressure. Thirty-one patients who had never been treated before for uncomplicated hypertension were studied. Each subject received a 30 mmol/per day sodium diet for 14 days, supplemented with a further 190 mmol of sodium in the first study week (220 mmol for the first 7 days and 30 mmol for the second 7 days). Throughout the study compliance was assessed by measuring daily urinary sodium excretion. Sodium sensitivity of blood pressure was defined as the difference (5% or more) between blood pressure at the end of the low and high sodium intake periods. On this basis 16 patients were defined as salt-sensitive (SS) and 15 patients as salt-resistant (SR). The two groups were homogeneous for age, sex and race. Baseline mean arterial pressure (MAP) was comparable between SS (108 +/- 1.8 mm Hg) and SR (107 +/- 2.1 mm Hg, P = NS). Each patient was submitted to M-MODE and two-dimensional echocardiogram studies in order to estimate left ventricular mass using the Penn conventional formula and parameters of left ventricular diastolic function. The left ventricular mass measurement showed higher values in the SS group although this did not reach statistical significance (118.4 +/- 4.4 vs 112.0 +/- 4.2 gr/mq, P = NS). Both interventricular septal and posterior wall thickness did not demonstrate significant differences between the two groups. The salt-sensitive group showed impaired left ventricular diastolic function; in particular, the first diastolic peak representing the early maximum of diastolic filling velocity (E) was lower in SS subjects than in SR subjects (71.6 +/- 2.9 vs83.1 +/- 3.3 cm/sec, P < 0.02). No significant difference was detected in the second peak representing the atrial maximum of filling velocity (A) (69.0 +/- 2.3 vs 66.0 +/- 2.0 cm/sec, P = NS). As a consequence the E/A ratio was significantly different (0.73 +/- 0.2 in the SR vs 1.2 +/- 0.04 in the SS group, P < 0.05). Moreover, the peak E integral was lower in SS than in SR subjects (8. 7 +/- 0.6 vs11.2 +/- 0.5 cm, P < 0.005; no difference for the peak A integral (6.0 +/- 0.3 vs 5.7 +/- 0.4 cm, P = NS). The E peak deceleration time was significantly reduced in the SS group (400.3 +/- 13.5 vs 500.9 +/- 12.8 cm/sec, P < 0.001). No significant difference was found for the isovolumetric relaxation time (IVRT) (95.7 +/- 4.3 vs 92.2 +/- 4.0, P = NS). Our data show an impaired diastolic function expressed by a reduced early diastolic filling velocity (peak E) and a significantly abnormal E/A ratio in SS in comparison with SR subjects. Therefore abnormalities in diastolic function are detectable earlier in SS hypertensive subjects than in SR irrespective of actual MAP.

Association between salt sensitivity and insulin concentrations in patients with hypertension.

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

The renin-aldosterone system and renal function in kidney transplantation.

Six renal transplant recipients, six uninephrectomized patients and six normal subjects were subjected to the physiological manoeuvre of head-out water immersion (WI), in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. The denervated, transplanted kidneys of the six patients were able to maintain a sodium excretory response to WI identical to that obtained in the controls (from 121 +/- 18 to 236 +/- 29 mumol/min, p < 0.005 vs 113 +/- 17 to 213 +/- 18 mumol/min, p < 0.005, respectively). Kidney transplant patients were also characterized by a preserved suppression of renin-aldosterone system (from 1.2 +/- 0.2 to 0.5 +/- 0.1 ng/ml/h, p < 0.03 and 12 +/- 1.0 to 7.0 +/- 1.0 ng/dl, p < 0.005, respectively) and stimulation of atrial natriuretic peptide (from 84 +/- 15 to 153 +/- 25 pg/ml, p < 0.05) to central hypervolemia by water immersion. The present study, while confirming the ability of the denervated kidney to handle sodium normally, also suggests that atrial natriuretic peptide could assume a crucial role in regulating renin secretion.

Water immersion and salt-sensitivity in essential hypertension.

It has been demonstrated that an exaggerated natriuretic response to central hypervolaemia is not necessarily associated with hypertension; many hypertensive subjects manifest either an appropriate or a blunted natriuresis in response to ECFV expansion attained by head-out water immersion. In this study, we tested the hypothesis that an underlying condition of salt-sensitivity may explain the heterogeneity of the natriuretic response of essential hypertension. Both salt-sensitivity tests and 2h water-immersion studies were randomly performed in 18 untreated essential hypertensives under a selected and controlled diet. Salt-sensitivity was defined as a significant drop in mean arterial pressure of 10% or greater, calculated as the difference between the average of the 25 readings under the high and the low salt period. Water immersion did result in a significant natriuretic and calciuretic response in the whole hypertensive group (n = 18, p < 0.001 and p < 0.05, respectively), while the examination of the individual excretion disclosed either exaggerated and appropriate or blunted urinary response. When the hypertensive group was classified in relation to salt-sensitivity, the greater fall in mean arterial pressure during low salt diet (salt-sensitivity) was associated with the more pronounced natriuretic response during water immersion (r = -0.66, p < 0.003). An identical correlation (r = -0.58, p < 0.01) was also found between changes in mean arterial pressure (low salt diet) and urinary calcium excretion (water immersion) in the same hypertensives. The water immersion-induced suppression of plasma aldosterone and the increase in plasma atrial natriuretic peptide did result from comparable magnitude in the salt-sensitive and in salt-resistant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium and sodium handling during volume expansion in essential hypertension.

To evaluate the actual role of extracellular fluid volume (ECFV) expansion per se in modulating the rate of urinary calcium excretion, a thermoneutral water immersion (WI) study was conducted in 10 normal subjects and 30 patients with essential hypertension. Central hypervolemia by 2 hours of WI caused a significant diuretic and natriuretic response (P < .005) in normal subjects; no significant changes were detected in urinary calcium and magnesium excretion. WI provoked either an appropriate or exaggerated natriuresis (P < .001) in 21 hypertensive patients; these subjects also exhibited a highly positive correlation between urinary sodium and calcium excretion during WI (P < .001). In the remaining nine hypertensive patients, WI produced a significant diuretic response, but a barely discernible (P = NS) natriuresis (inappropriate response). These subjects also exhibited a significant reduction of urinary calcium (P < .001) and magnesium (P < .01) excretion. The data indicate that (1) volume expansion per se may have a role in regulating calcium excretion in hypertensive subjects; (2) a calcium leak may be attributable to a close relationship between urinary sodium and calcium metabolism, and causally related to a disturbance of sodium and volume homeostasis in hypertension.

Regulation of sodium excretion in human hypertension: long-term effects of calcium antagonist and angiotensin converting enzyme inhibitor.

Fourteen subjects with untreated essential hypertension were subjected to 2-h water immersion (WI) study. They were then randomly assigned to two distinct oral antihypertensive regimens with either calcium-channel blocker nifedipine (group 1, n = 7) or the angiotensin-converting enzyme (ACE) inhibitor lisinopril (group 2, n = 7). Three months later, a WI study identical to the first was repeated in the same hypertensive subjects. In group 1, treatment with nifedipine gastrointestinal therapeutic system (30 mg daily) significantly enhanced the natriuretic response to volume expansion by WI (peak value 405 +/- 82 mumol/min during WI plus nifedipine vs. 291 +/- 52 mumol/min during WI alone, p < 0.05). In group 2, treatment with lisinopril (20 mg daily) was associated with a blunted natriuretic response to volume expansion by WI (peak value 189 +/- 54 mumol/min during WI plus lisinopril vs. 320 +/- 53 mumol/min during WI alone; p < 0.025). A significant direct correlation between urinary sodium excretion (delta UNa V) and mean arterial pressure (delta MAP) was noted during WI plus nifedipine. Each long-term drug treatment was associated with a decrease in BP and hormonal changes of the same magnitude. Our data suggest that calcium antagonists could act as "diuretic agents" capable of counteracting the antinatriuretic effect of reduced renal perfusion pressure.

Renin-angiotensin system unresponsiveness in phaeochromocytoma.

Water immersion to the neck is able to provoke a profound suppression of the renin-angiotensin system in several clinical conditions associated with hyper-reninaemia. Both hyper-reninaemia and secondary aldosteronism have sometimes been described in phaeochromocytoma. We report on two patients, with surgically proven phaeochromocytoma, in whom water immersion, performed before surgery, failed to induce any significant change in plasma renin activity.

A new diagnostic test for primary aldosteronism.

Isotonic-isooncotic central volume expansion by head-out water immersion was induced in six aldosterone-producing adenoma subjects and in six patients with idiopathic hyperaldosteronism. Plasma renin activity and plasma aldosterone levels did not significantly change during water immersion while serum cortisol was significantly suppressed (P less than .001) and the aldosterone-cortisol ratio increased (P less than .02) in aldosterone-producing adenoma patients. Water immersion also revealed the failure of plasma aldosterone levels to decrease below 10 ng/dL in these subjects, thus confirming previous results obtained during isotonic saline infusion. Otherwise, plasma renin activity and plasma aldosterone were significantly reduced (P less than .05 and P less than .01 respectively) by water immersion and plasma aldosterone invariably fell below 10 ng/dL in patients with idiopathic aldosteronism. In view of the diagnostic reliability of such a suppression test we conclude that water immersion is suitable for discriminating between the two forms of primary aldosteronism. We therefore suggest its use for assessing renin-aldosterone responsiveness in primary aldosteronism.

Sodium homeostasis and hormonal responses during dopaminergic blockade in normal humans.

Six normal subjects were submitted to 2 h water immersion (WI) with and without pharmacological dopaminergic (DA) blockade with metoclopramide (MCP). Urinary sodium excretion showed a marked increase during WI alone while it was blunted during WI plus DA blockade. Plasma aldosterone was significantly suppressed by WI alone but remained unchanged during WI plus MCP. Plasma atrial natriuretic factor showed similar augmentation during WI alone and during WI plus MCP. The reduced sodium and 6-keto-PGF1 alpha excretion, observed during WI plus MCP administration, suggests that dopamine might induce prostacyclin synthesis in the kidney during WI.

The antinatriuretic effect of dopaminergic blockade during volume expansion is independent of circulating atrial natriuretic factor.

1. Ten normal subjects were subjected to 2 h water immersion with and without pharmacological dopaminergic blockade with either metoclopramide (group I) or domperidone (group II). 2. In group I, urinary sodium excretion showed a marked increase during water immersion alone, whereas it was blunted during water immersion plus dopaminergic blockade with metoclopramide (P less than 0.05 vs water immersion alone, n = 5). Plasma aldosterone was significantly suppressed by water immersion alone (P less than 0.05), but remained unchanged during water immersion plus metoclopramide. Plasma atrial natriuretic factor showed similar augmentation during water immersion alone and during water immersion plus metoclopramide. 3. Another five subjects (group II) were studied during water immersion alone and during water immersion plus dopaminergic blockade with domperidone. In this group the increase in urinary sodium excretion was similarly blunted by dopaminergic blockade. Plasma atrial natriuretic factor was equally elevated during water immersion alone and during water immersion plus domperidone, but aldosterone was suppressed by both water immersion alone and water immersion plus domperidone. 4. Our findings suggest that water immersion-induced atrial natriuretic factor release is independent of dopaminergic activity. Dopamine blockade is able to blunt significantly both water immersion-induced natriuresis and plasma aldosterone suppression, independently of the marked elevation of circulating atrial natriuretic factor, via a mechanism involving type 2 dopaminergic receptors.

Role of renal hemodynamics in the exaggerated natriuresis of essential hypertension.

Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essential hypertensives and six normotensive healthy controls. Before and during WI we measured mean arterial pressure (MAP), urine flow (V/min), sodium (UNaV) and potassium (UKV) excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and intrarenal (wedged) venous pressure (IRVP). In comparison with normotensive controls, the exaggerated natriuretic response in hypertensives (P less than 0.05 for UNaV during WI) was associated with an enhanced vasodilating response as demonstrated by a greater increase in ERPF (P less than 0.05) and by a more pronounced fall in calculated renal precapillary resistances (P less than 0.05). A more significant increase in IRVP was found in hypertensive group (P less than 0.05). Glomerular filtration rate (GFR) did not change in either group during WI. MAP, unchanged in normotensives, was significantly reduced in hypertensives (P less than 0.05), while remaining in the hypertensive range. These findings suggest that intrarenal physical factors play a major role in determining the exaggerated natriuresis during WI in hypertensive man.

Circulating opioid peptides during water immersion in normal man.

1. This study was designed to evaluate variations in plasma beta-endorphin, methionine-enkephalin, adrenocorticotropic hormone and serum prolactin in healthy volunteers during head-out water immersion. 2. Water immersion induced an increase in methionine-enkephalin plasma levels, which was associated with a significant fall in mean arterial pressure and heart rate. 3. Conversely, a suppression of plasma beta-endorphin, adrenocorticotropic hormone and serum prolactin was detected during water immersion. 4. We suggest that a dopaminergic inhibitory control mechanism may be involved in regulating circulating levels of beta-endorphin, adrenocorticotropic hormone and prolactin in normal subjects undergoing extracellular fluid volume expansion produced by water immersion.

Dopamine blockade abolishes the exaggerated natriuresis of essential hypertension.

We studied natriuresis during central hypervolaemia by immersing eight normal subjects and eight patients with uncomplicated essential hypertension up to the neck in water, either in the absence (study 1) or presence (study 2) of dopamine blockade by metoclopramide. Water immersion without metoclopramide induced an exaggerated natriuresis in hypertensives compared with normotensives (P less than 0.001). This occurred in the presence of identical hormonal (plasma renin activity, plasma aldosterone and prolactin), renal (creatinine clearance) and pressor responses in both groups (study 1). The marked natriuresis seen during water immersion alone in normotensives was significantly blunted (P less than 0.02) but not abolished during water immersion with addition of metoclopramide. On the other hand, the exaggerated natriuresis found in hypertensives during water immersion alone was completely abolished during water immersion plus dopamine blockade by metoclopramide (study 2). Similar hormonal, renal and pressor changes were detected in both normotensive and hypertensive subjects during water immersion plus metoclopramide administration. Our data demonstrate that metoclopramide abolishes the exaggerated natriuretic response seen in hypertensives during volume expansion produced by water immersion, and suggest that dopamine may play a critical role in mediating the hypernatriuresis of essential hypertension.

Influence of cardiopulmonary receptors on the bradycardic responses to carotid baroreceptor stimulation in man.

Animal studies have shown that arterial baroreflexes are modulated by reflexes originating from the cardiopulmonary volume receptors, and that this modulation consists of a reduction of the inhibitory influence exerted by arterial baroreceptors on the heart and peripheral circulation. This has not been confirmed in man, however, in whom no reduction in the bradycardic response to carotid baroreceptor stimulation has been observed after the mild increase in central venous pressure (right atrial catheter) and cardiopulmonary receptor activity provided by passive leg raising. In seven normotensive subjects carotid baroreceptors were gradedly stimulated by progressively increasing carotid transmural pressure through a neck chamber device, the resulting reflex lengthening in R-R interval being measured in the two-three cardiac cycles immediately after the baroreceptor stimulus. This manoeuvre was performed in control conditions and repeated during a head-out water immersion which increased central venous pressure (right atrial catheter) from 1.5 +/- 0.2 to 12.0 +/- 0.9 mmHg (mean +/- SE), thereby providing a marked increase in the cardiopulmonary receptor stimulus. In the control condition graded stimulation of the baroreceptors caused a progressive lengthening in R-R interval, the maximal effect being + 477.4 +/- 57.2 ms. Immersion increased the R-R interval from 774.2 +/- 3.2 to 961.6 +/- 5.8 ms (P less than 0.01) and reduced mean arterial pressure (cuff measurement) from 96.0 +/- 1.0 to 82.3 +/- 0.9 mmHg. The changes in R-R interval induced by carotid baroreceptor stimulation were virtually identical with those observed in the absence of immersion.

Renal hemodynamics and natriuresis during water immersion in normal humans.

The renal vascular and functional responses to acute "central hypervolemia" by water immersion to the neck were determined in six normal subjects. During isotonic-isooncotic expansion by water immersion there was a significant increase in urine flow from 1.1 +/- 0.1 to 6.9 +/- 1.0 ml/min (p less than 0.05) and sodium excretion from 99.1 +/- 8.8 to 300 +/- 28 mu Eq/min (p less than 0.05). Glomerular filtration rate did not change while renal blood flow significantly increased during water immersion. Deep intrarenal venous pressure (IRVP) increased from 18.2 +/- 1.4 to 32 +/- 1.7 mmHg (p less than 0.05) while mean arterial pressure was unchanged. This marked natriuresis seen during water immersion was associated with reduced renal vascular resistance and increased deep intrarenal venous pressure demonstrating that continued natriuresis could relate to increased capillary hydrostatic pressure.

Dopamine blockade and natriuresis during water immersion in normal man.

Natriuresis was studied during water immersion in eight normal subjects either in the absence or in the presence of dopamine blockade by domperidone. Creatinine clearance showed no significant changes; urine flow remained significantly above control values during water immersion, implying persistent suppression of antidiuretic hormone. The marked natriuresis seen during water immersion alone was significantly blunted (P less than 0.05) but not abolished during water immersion plus domperidone. Suppression of the renin-aldosterone system by water immersion alone was not significantly different from that obtained during water immersion plus dopamine blockade. On the contrary, plasma prolactin levels, previously suppressed during water immersion alone, were significantly stimulated during water immersion plus domperidone, thus indirectly suggesting a role of dopamine in mediating the blunted natriuresis seen during water immersion.

Renin-aldosterone system suppression during water immersion in renovascular hypertension.

We studied renin-aldosterone system behaviour in five renovascular hypertensive patients during central hypervolaemia by water immersion to the neck. Water immersion significantly suppressed the high peripheral renin levels of the patients despite an autonomic renin secretion from the stenotic kidney, a significant reduction of mean blood pressure and an increase in distal tubule sodium concentration. The effect of immersion on plasma aldosterone appeared to be primarily mediated via suppression of plasma renin activity (PRA). Our data suggest that: (a) the renin secretion is mainly modulated by cardiopulmonary receptors activity; (b) the neurogenic reflex control of plasma renin activity is very effective in renovascular hypertension.

Cardiovascular, baroreflex and humoral responses in hypertensive patients during nicardipine therapy.

Cardiovascular, baroreflex and humoral responses were evaluated in 8 patients with essential hypertension during a control period and then after oral treatment for 5 days with nicardipine hydrochloride 60 mg/d, a calcium channel antagonist. Systolic, diastolic and mean arterial cuff pressures fell after the treatment from 145.7, 98.6 and 114 mmHg control to 136.5, 86.1 and 102.9 mmHg. Heart rate increased from 71 to 78.7 beats/min indicating activation of the baroreflex control mechanism. Neurally mediated changes in the cardiovascular responses to an increase in carotid baroceptor activity and to dynamic exercise were not affected by the drug, nor was the renin-aldosterone system. Thus, a clinically dose of nicardipine significantly reduced mean arterial pressure, whilst preserving circulatory homeostasis.

Low-pressure receptor activity and exaggerated natriuresis in essential hypertension.

Urinary sodium excretion, central hemodynamics, and mean arterial pressure (MAP) were studied in 7 normal subjects and 19 hypertensive patients during both central hypervolemia by water immersion to the neck (NI) and extracellular volume expansion by i.v. saline infusion. During 2-hour NI, 12 out of the 19 hypertensives exhibited a significant fall in MAP (p less than 0.001). Exaggerated natriuresis did not occur in these patients (ns). In the remaining 7 hypertensive patients in whom, during NI, MAP was unchanged, exaggerated natriuresis was found (p less than 0.001). During saline infusion, MAP was either unchanged or increased and exaggerated natriuresis was found in all hypertensive patients (p less than 0.001) previously submitted to NI. Our findings suggest that a high MAP is a major determinant of exaggerated natriuresis in arterial hypertension.