Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express receptors for Ang II, the Ang II binding site has not been characterized with radioligand binding techniques. We therefore used iodine 125-labeled Ang II to monitor Ang II-receptor density during differentiation of a mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed a single class of high-affinity binding sites (dissociation constant approximately 3 nmol/L) in both differentiated and nondifferentiated cells. During differentiation, the density of Ang II-receptor sites increased roughly 15-fold in differentiated podocytes (maximal density of specific binding sites 881 fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B, and AT2 receptor subtypes, and competitive binding studies found that differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor number was associated with increased Ang II-receptor responsiveness, as evidenced by enhanced Ang II-stimulated inositol phosphate (IP) generation and incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP generation were mediated by AT1-receptor activation. These data suggest that glomerular podocytes express a high-affinity binding site for Ang II with pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site is up-regulated during podocyte differentiation, and receptor activation induces both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate that activation of podocyte Ang II receptors contributes to glomerular damage in disease states. 相似文献
Submaximal field tests are especially recommended when repeated testing is warranted. This study aimed at assessing the validity of the submaximal versions of the Yo-Yo intermittent tests in male recreational football players in untrained and trained status. The participants’ (n = 66; age 39.3 ± 5.8 years, VO2max 41.2 ± 6.2 mL·kg−1·min−1, body mass 81.9 ± 10.8 kg, height 173.2 ± 6.4 cm) heart rate after 2 minutes (HR2min) during the level 1 (YYIE1HR2min) and 2 (YYIE2HR2min) versions of the Yo-Yo intermittent endurance test and the level 1 version of the Yo-Yo intermittent recovery test (YYIR1HR2min) was plotted against individual VO2max values. Thirty-two participants performed all the tests after a 12-week recreational football intervention for test responsiveness. Associations between VO2max and YYIE1HR2min were large to small (P = .0001). Large to trivial associations were found between YYIE2HR2min, YYIR1HR2min, and VO2max (P < .01). Maximal Yo-Yo performances were large, significant, and inversely related to HR2min (−0.68 to −0.49, P < .0001). Pre- to post-intervention ICC values were good for YYIE1HR2min and YYIE2HR2min, and excellent for YYIR1HR2min. Post-intervention associations between HR2min and Yo-Yo maximal performances were large to very large (−0.55 to −0.72; P < .002, n = 32). Training-induced changes in VO2max moderately correlated with YYIR1HR2min (−0.48; P = .007; n = 32). HR2min lower than 89%, 98%, and 91% HRmax for YYIE1HR2min, YYIE2HR2min, and YYIR1HR2min, respectively, may be considered as signs of good to excellent VO2max levels. Since in the YYIE1HR2min, the participants attained 84% HRmax and test specificity increased for HR2min values <89%, this test may be the preferred choice when repeated assessment of aerobic fitness, using submaximal intermittent Yo-Yo tests, is considered in recreational football. 相似文献
Objectives. We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings.
Background. In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate–pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear.
Methods. We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, ≥70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized.
Results. Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = −0.22, 95% CI −0.44 to −0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = −0.25, 95% CI −0.47 to −0.01, p < 0.05) and the redistribution gradient (r = −0.33, 95% CI −0.53 to −0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent.
Conclusions. In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.
The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN — a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four classical antiepileptic drugs (AEDs: clonazepam [CZP], ethosuximide [ETS], phenobarbital [PB], and valproate [VPA]) in the mouse pentylenetetrazole (PTZ)-induced clonic seizure model.WIN (15 mg/kg, i.p.) significantly enhanced the anticonvulsant action of ETS, PB and VPA, but not that of CZP against PTZ-induced clonic seizures. The ED50 values of ETS, PB and VPA were reduced from 148.0, 13.9 and 137.1 mg/kg to 104.0, 8.3 and 85.6 mg/kg, respectively (P < 0.05). WIN (5 and 10 mg/kg, i.p.) had no impact on the anticonvulsant action of all studied AEDs against PTZ-induced clonic seizures. WIN (15 mg/kg, i.p.) significantly elevated total brain concentrations of ETS and VPA, but not those of CZP and PB in mice. Moreover, WIN combined with CZP, ETS, PB and VPA significantly impaired motor performance, long-term memory and muscular strength in mice subjected to the chimney, passive avoidance and grip-strength tests, respectively.Pharmacodynamic enhancement of the anticonvulsant action of PB by WIN against PTZ-induced clonic seizures is favorable from a preclinical viewpoint. Advantageous effects of WIN in combination with ETS and VPA against PTZ-induced seizures were pharmacokinetic in nature. However, WIN combined with CZP, ETS, PB and VPA impaired motor coordination and long-term memory as well as reduced skeletal muscular strength in the experimental animals. 相似文献
We prospectively studied the dose‐dependent effect of transfused stored red blood cells (RBCs) on recipient RBC indices, deformability and cell density in 10 patients administered stored RBCs for blood transfusion during general surgery. There were dose‐dependent decreases in mean corpuscular volume and increases in mean corpuscular haemoglobin concentration after completion of 4‐ and 6‐unit stored RBC transfusions. The amount of dense populations increased proportionately with the amount of stored RBCs transfused. The maximal deformability index value was significantly and dose‐dependently decreased, suggesting that hemodynamic blood flow, especially the microcirculation may be impaired in patients who receive large amounts of stored RBCs. 相似文献