Capillary growth, ultrastructure remodelling and exercise training in skeletal muscle of essential hypertensive patients

AIM The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. METHODS To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. RESULTS At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). CONCLUSION Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.

Redox front geochemistry and weathering: theory with application to the Osamu Utsumi uranium mine, Poços de Caldas, Brazil

Numerical calculations describing weathering of the Poços de Caldas alkaline complex (Minas Gerais, Brazil) by infiltrating groundwater are carried out for time spans up to two million years in the absence of pyrite, and up to 500,000 years with pyrite present. Deposition of uranium resulting from infiltration of oxygenated, uranium bearing groundwater through the hydrothermally altered phonolitic host rock at the Osamu Utsumi uranium mine is also included in the latter calculation. The calculations are based on the quasi-stationary state approximation to mass conservation equations for pure advective transport. This approximation enables the prediction of solute concentrations, mineral abundances and porosity as functions of time and distance over geologic time spans. Mineral reactions are described by kinetic rate laws for both precipitation and dissolution. Homogeneous equilibrium is assumed to be maintained within the aqueous phase. No other constraints are imposed on the calculations other than the initial composition of the unaltered host rock and the composition of the inlet fluid, taken as rainwater modified by percolation through a soil zone. The results are in qualitative agreement with field observations at the Osamu Utsumi uranium mine. They predict a lateritic cover followed by a highly porous saprolitic zone, a zone of oxidized rock with pyrite replaced by iron-hydroxide, a sharp redox front at which uranium is deposited, and the reduced unweathered host rock. Uranium is deposited in a narrow zone located on the reduced side of the redox front in association with pyrite, in agreement with field observations. The calculations predict the formation of a broad dissolution front of primary kaolinite that penetrates deep into the host rock accompanied by the precipitation of secondary illite. Secondary kaolinite occurs in a saprolitic zone near the surface and in the vicinity of the redox front. Gibbsite forms a bi-modal distribution consisting of a maximum near the surface followed by a thin tongue extending downward into the weathered profile in agreement with field observations. The results are found to be insensitive to the kinetic rate constants used to describe mineral reactions.

Redox modulation of STIM-ORAI signaling.

STIM1 and ORAI1 constitute the core machinery of the ubiquitous store-operated calcium entry pathway and loss of function in these proteins is associated with severe immune and muscular disorders. Other isoforms-STIM1L, STIM2, ORAI2 and ORAI3 exhibit varied expression levels in different cell types along with several other interaction partners and thereby play different roles to facilitate, regulate and fine-tune the calcium entry. STIM proteins convey the Ca(2+) store-depletion message to the PM and thereby participate in refilling of the ER by physically interacting with the Ca(2+)-selective ORAI channels at the PM. STIM and ORAI are exposed to oxidative modifications in the ER, the cytosol, and at the cell surface, and redox-mediated alterations in STIM/ORAI coupling might contribute to autoimmune disorders and cancer progression. This review discusses the redox reactivity of cysteine residues in STIM and ORAI isoforms, focusing on the oxidative modifications of STIM and ORAI proteins by which STIM-ORAI signaling can be modulated.