Nongenomic effects of aldosterone on phosphocreatine levels in human calf muscle during recovery from exercise.

Nongenomic in vitro effects of aldosterone on the sodium-proton antiport and intracellular second messengers have been described in human mononuclear leukocytes, vascular smooth muscle cells, and endothelial cells. To test the potential physiological relevance of these effects, an in vivo 31P magnetic resonance spectroscopy study on the human calf at rest and during exercise was performed in 10 healthy volunteers receiving either 1 mg aldosterone or placebo iv in a double blind, randomized, cross-over trial. Spectra were analyzed for phosphocreatine, ATP, phosphomonoesters, inorganic intracellular phosphate, and intracellular pH. Resting values remained unchanged by aldosterone. After isometric contraction of the calf (50% body weight for 3 min), phosphocreatine recovered to significantly higher levels after application of aldosterone compared with placebo. Other parameters were not significantly changed by aldosterone. Effects appeared immediately after isometric contraction and, thus, occurred within 8 min of aldosterone administration. They are, therefore, likely to represent the first contemporary evidence of nongenomic in vivo effects of aldosterone in man. These findings also point to an involvement of aldosteron in the acute stress adaptation of cellular oxidative metabolism in human muscle physiology

Regulation of natriuretic peptide (urodilatin) release in a human kidney cell line

Regulation of natriuretic peptide (urodilatin) release in a human kidney cell line.BackgroundTo identify the molecular mechanisms underlying the release of a renal natriuretic peptide (NP) we selected a human kidney cell line (HEK 293) that displays several characteristics of distal tubular cells.MethodsCells were exposed to different extracellular and intracellular stimuli, and the effect on NP release was measured with a specific urodilatin radioimmunoassay, as well as with an atrial NP (ANP) radioimmunoassay.ResultsIn the absence of stimuli, HEK 293 cells showed a basal release of urodilatin immunoreactivity and ANP immunoreactivity. Raising the osmolality of the secretion medium with sodium chloride and various other osmolytes rapidly increased cellular NP secretion. Elevation of intracellular cAMP levels by forskolin plus 3-isobutyl-1-methylxanthine and administration of phorbol-12-myristate-13-acetate together with the calcium-ionophore A23187 also resulted in respective increases in the amount of secreted peptide. HEK 293 cells exhibit the endogenous expression of both particulate and soluble guanylyl cyclases. In the presence of 8-Br-cGMP, cell cultures showed the enhanced secretion of an ANP immunoreactive peptide only, indicating that guanylyl cyclase activation provoked the secretion of ANP immunoreactivity but not of urodilatin immunoreactivity.ConclusionsThe human embryonic kidney cell line HEK 293 represents a renal cellular model system in which we have identified a rapid and regulated release of NPs in response to the osmotic effect of increased extracellular sodium chloride and various intracellular stimuli

Verapamil impairs secretion of stimulated atrial natriuretic factor in humans

AbstractThe adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I.Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations.Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor

Эксплуатационная надежность силовых трансформаторов с масляным охлаждением напряжением 6-35кВ

В работе рассмотрены основные неисправности трансформаторов с масляным охлаждением. Повреждения представлены в виде диаграмм. Также произведен расчет основных величин эксплуатационной надежности.The main problems of transformers with oil cooling are considered. Damage is presented in the form of diagrams. The basic values ??of operational reliability were also calculated

NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272

BACKGROUND: The most important receptor for nitic oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase. RESULTS: We developed a photoaffinity label ((3)H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of (3)H-meta-PAL together with the highly purified sGC leads to a covalent binding to the α(1)-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the (3)H-meta-PAL labeled sGC was fragmented by CNBr digest. The (3)H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236–290 of the α(1)-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the (3)H-meta-PAL. CONCLUSIONS: Our data demonstrate that the region surrounding the cysteines 238 and 243 in the α(1)-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators