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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−1NG-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.

Background Professional athletes exhibit lower left ventricular wall thicknesses, diameters and mass (in females), with less frequent training-related electrocardiogram (ECG) changes, as compared with controls.Methods We studied the association of sex with left ventricular structure in trained early adolescents. Two hundred and six adolescent Caucasian athletes (mean age 13.8 ± 1.6, range 11.8–16.9 years, 158 males and 48 females), with similar degree of training underwent ECG and echocardiographic measurements of left ventricular diameters, thicknesses and mass, with relative wall thickness as the remodelling index.Results As compared with females, males exhibited greater maximal wall thickness (males = 8.7 ± 1.2 vs. females = 7.9 ± 0.8) and indexed left ventricular mass (100 ± 18 g/m2vs. 79 ± 12, p< 0.001), without differences in relative wall thickness (males = 0.35 ± 0.04 vs. females = 0.34 ± 0.04) and with higher prevalence of ECG-based left ventricular hypertrophy, sinus bradycardia and ST-elevation. An analysis of covariance, using age, body surface area, systolic blood pressure, heart rate and sex as the covariates, reported that sex is a strong predictor of left ventricular mass, maximal wall thickness, left ventricular diastolic diameter and ECG-based left ventricular hypertrophy. In a binary logistic regression model analysis sex, like left ventricular mass, predicted ST-trait elevation.Conclusions Our results suggest that, in early adolescence, female athletes have lower left ventricular mass and thicknesses compared with males, without geometrical differences. Therefore, sex, independent of age, is a strong determinant of structural parameters also in early adolescent athletes. These data indicate that sex-specific parameters are needed in the pre-participation cardiovascular screening of adolescent athletes.

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−1NG-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−1l-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−2C, +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.