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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/m2) 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. [ABSTRACT FROM AUTHOR]

Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 μg·kg -1 ·min -1 N G -nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2αV; an oxidative stress marker) were measured. With PL + l -NAME, the following changes were observed: +6% MAP ( P < 0.005 vs. baseline), -10% GFR, -20% RBF, -49% UNaV ( P < 0.001), and +120% U8-iso-PGF2αV ( P < 0.01). In contrast, MAP did not increase during LOS + l-NAME or MANI + l-NAME ( P > 0.05 vs. baseline), whereas renal changes were the same during LOS + l-NAME vs. PL + l-NAME (ANOVA, P > 0.05). However, during MANI + l-NAME, changes vs. baseline in GFR (-6%), RBF (-12%), and UNaV (-34%) were blunted vs. PL + l-NAME and LOS + l-NAME ( P < 0.005), and the rise in U8-iso-PGF2αV was almost abolished (+37%, P > 0.05 vs. baseline; P < 0.01 vs. PL + l-NAME or LOS + l-NAME). We conclude that, since MANI blunted l-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2αV was essentially prevented during MANI + l-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability., (Copyright © 2017 the American Physiological Society.)

The objective is to elucidate the effect of nitric oxide (NO)-renin-angiotensin system (RAS) interactions on renal hemodynamic function in uncomplicated, type 1 diabetes mellitus (DM). In 14 salt-replete, male healthy volunteers (C) and 9 male DM patients on euglycemia, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), and sodium excretion (UNaV) were measured at baseline and during a 90-min infusion of 3.0 μg·kg⁻¹·min⁻¹ NG-nitro-L-arginine-methyl-ester (L-NAME) after 3 days of pretreatment with either placebo (PL) or 50 mg losartan (LOS). Baseline GFR, RBF, and FF were higher in DM (P < 0.005). In the C group, PL + L-NAME caused declines in GFR (101 ± 3 to 90 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (931 ± 22 to 754 ± 31 ml·min⁻¹·1.73 m⁻²), and UNaV (158 ± 12 to 82 ± 18 μmol/min) and an increase in FF (0.19 ± 0.02 to 0.21 ± 02; P < 0.001), which were not influenced by LOS pretreatment (P > 0.05 for LOS + L-NAME-C vs. PL + l-NAME-C). In DM, PL + L-NAME resulted in exaggerated renal effects, with changes in GFR (128 ± 3 to 104 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (1,019 ± 27 to 699 ± 34 ml·min⁻¹·1.73 m⁻²), UNaV (150 ± 13 to 39 ± 14 μmol/min), and FF (0.22 ± 0.03 to 0.26 ± 0.02) that were significantly greater vs. PL + L-NAME-C (P < 0.005). LOS pretreatment blunted GFR, RBF, FF, and UNaV responses to L-NAME in DM (P < 0.005 vs. PL + L-NAME-DM), resulting in a response profile that was similar to PL + L-NAME and LOS + L-NAME in C (P > 0.05). Renal responses to L-NAME in uncomplicated, type 1 DM are exaggerated vs. C, consistent with an upregulation of NO bioactivity. LOS, without effects in C, prevents the accentuated actions of L-NAME in DM, thus indicating an augmented role for NO-RAS interactions in renal hemodynamic function in DM.

According to the "tubulocentric" hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute "distal" sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg(-1)·min(-1) l-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (-0.26 ± 0.07 mmol/min C vs. -0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min(-1)·1.73 m(-2)) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min(-1)·1.73 m(-2)). In contrast, with ARG.HCl, DDNa rose in both groups (P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased (P = 0.001, +219 ± 20 ml·min(-1)·1.73 m(-2) C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups (P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C (P = 0.001) and GFR, unchanged in C, declined in DM (-7.4 ± 0.9 ml·min(-1)·1.73 m(-2), P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction.

To investigate whether bradykinin (BK) participates in the inhibition of renal effects of exogenous angiotensin II (AngII) by AngII type 1 receptor (AT1R) blockade, eight salt-repleted volunteers underwent four p-aminohippurate- and inulin-based renal studies of AngII infusion at increasing rates of 0.625, 1.25, and 2.5 ng.kg.min(-1) for 30 min. Studies 1 and 2 were preceded by 3 days of placebo, whereas studies 3 and 4 used 240 to 320 mg.day(-1) valsartan. Bradykinin B2-type receptor (BKB2R) antagonist icatibant (50 mug.kg(-1)) was coinfused in studies 2 and 4. Mean blood pressure (MBP), glomerular filtration rate (GFR), renal blood flow (RBF), and renal sodium excretion (UNaV) were measured. In study 1, MBP rose by 12.8%, UNaV decreased by 68%, and GFR and RBF also fell (p < 0.001 for all). In study 2, GFR and RBF fell as in study 1, but the rise in MBP and the fall in UNaV were accentuated [+20.0%, analysis of variance (ANOVA), p < 0.02 versus study 1 and -80.0%, p < 0.05, respectively]. In study 3, AngII had no effects, and in study 4, renal hemodynamics remained unaffected, but MBP still rose and UNaV fell (ANOVA, p < 0.02 and 0.005 versus study 3, respectively). Icatibant accentuated AngII-induced changes in MBP and UNaV. Previous AT1R blockade prevented any systemic and renal effects of AngII, but significant changes in MBP and UNaV still followed AngII plus icatibant even after AT1R blockade. BK, through BKB2Rs, participates in the inhibitory action of AT1R blockers toward actions of exogenous AngII on MBP and UNaV in healthy humans.

Aim of this work is to illustrate how analytical interference in immunoassay may produce serious errors in clinical laboratory results. The sophisticated quality assurance schemes used in many laboratories do not identify erroneous results arising from aberrant samples. Recently attention has been focused on the incidence and implication of false-positive results arising from the presence of certain substances in a patient's serum that interfere with one or more steps in immunoassays. In this paper, we present the case of a 92 year-old woman whose plasma myoglobin concentrations falsely increased when measured using the Beckman Access assay. We demonstrated that heterophilic antibodies accounted for the falsely increased myoglobin values, and we suggest how to resolve such situations.

Objective: To investigate whether changes in tubuloglomerular feedback (TGF) dependent upon the tubular effects of buffering anions affect the renal haemodynamic response to L-arginine in healthy (control) individuals and patients with essential hypertension., Methods: Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF) and fractional excretion of sodium (FENa), chloride (FECl) and lithium (FELi) were measured in 10 control individuals and 10 hypertensive patients during two 3-h infusions of 0.012 mmol/kg per min L-arginine buffered with either HCl or citric acid., Results: FELi, FECl and FENa increased (P < 0.001) comparably in controls and hypertensive individuals with arginine-HCl and decreased with arginine-citrate (P < 0.001). MAP was unchanged in controls with arginine-HCl and decreased by 3% with arginine-citrate (P < 0.001), and decreased in hypertensive individuals with both arginine-HCl and arginine-citrate (by 3 and 7%, respectively; P < 0.001). GFR increased with arginine-citrate in controls and hypertensive individuals (by 6.1 and 5.4%, respectively; P < 0.001), but did not change with arginine-HCl in controls and declined by 4.6% in hypertensive individuals (P < 0.05). RBF increased equally after arginine-citrate in controls and hypertensive individuals (by 34 and 33%, respectively; P < 0.001); it also increased after arginine-HCl (22 and 13%, respectively; P < 0.001), but less than after arginine-citrate (P < 0.001), and 41% less in hypertensive individuals than in controls (P < 0.001)., Discussion: Because arginine-HCl, unlike arginine-citrate, inhibits tubular reabsorption and elicits much less renal vasodilatation than does arginine-citrate, renal haemodynamics in response to L-arginine are modulated by changes in reabsorption and TGF according to the tubular effects of the attendant anion. As renal vasodilatation in hypertensive individuals was reduced only with arginine-HCl, which activates TGF, the blunted vasodilatation of the hypertensive kidney in response to arginine-HCl reflects an exaggerated response to an activated TGF.

To investigate whether endothelin-A receptors mediate hemodynamic changes caused by exogenous Angiotensin II in humans, 7 healthy volunteers on a 250-mmol sodium diet underwent 3 separate p-aminohippurate and inulin-based renal hemodynamic studies. In 2 studies, Angiotensin II (increasing rates of 0.625, 1.25, and 2.5 ng/kg per minute, each for 30 minutes) was infused either alone or combined with endothelin-A blocker, BQ123, 0.4 nmol/kg per minute. A third infusion of BQ123 alone was not followed by any change. Angiotensin II infusion alone produced a progressive decrease in renal blood flow (1080+/-94 mL/minx1.73 m2 to 801+/-52, P<0.001, versus baseline) and glomerular filtration rate (115+/-7 mL/minx1.73 m2 to 97+/-7, P<0.001) with increase in filtration fraction (0.188+/-.017 to 0.220+/-.030, P<0.01). Mean arterial pressure and renal vascular resistance increased markedly (86.8+/-3.1 to 97.5+/-4.4 mm Hg, P<0.001 and 83+/-7 to 133+/-20 mm Hg/min per liter, P<0.001, respectively). With Angiotensin II+BQ 123, mean arterial pressure still rose (86.2+/-3.1 to 91.1+/-4.3, P<0.05 versus both baseline and BQ123 alone) but significantly less than with Angiotensin II alone (P<0.05). Renal blood flow (1077+/-76 to 993+/-79, P<0.001) and glomerular filtration rate (115+/-7 to 105+/-7, P<0.05) also changed to a significantly lesser extent than with Angiotensin II alone (P<0.05 for both), whereas filtration fraction remained unchanged (0.185+/-.015 to 0.186+/-.016). Renal vascular resistance rose only by 17% (82+/-5 to 95+/-9, P<0.001 versus baseline as well as versus BQ123 or Angiotensin II alone). The results show that endothelin through Endothelin-A receptors contributes substantially to the systemic and renal vasoconstriction of low-dose exogenous Angiotensin II in healthy humans.

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 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.

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.

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.

In 25 patients with essential hypertension and 9 control subjects we have studied the effects of central hypervolemia during water immersion on both renin-angiotensin-aldosterone system and renal function (diuresis volume and urine excretion of Na, k and osmoles). Reduction of blood pressure, plasma renin activity and aldosterone was found to be similar in both groups; renal excretion of water, Na, K and osmoles was significantly higher in the hypertensive group compared to the controls. These urinary features may be related to a reduced proximal tubular reabsorption by cardiorenal reflex due to cardiopulmonary volume receptors stimulation without any change of GFR measured as the creatinine clearance. The urinary pattern, observed during water immersion in hypertensive group without any change of plasma sodium, osmolality or protein concentration, was comparable to "exaggerated natriuresis"; this may suggest that also "exaggerated natriuresis" is due either to renal vasodilatation or to renal tubular sympathetic activity reduction secondary to a cardiorenal reflex by cardiopulmonary volume expansion.

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.

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.

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.

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.