Inhibition of angiotensin type 1 receptor impairs renal ability of K conservation in response to K restriction.
ABSTRACT We have previously demonstrated that ANG II inhibits ROMK-like small-conductance K channels (SK) in the cortical collecting duct from rats on a K-deficient diet (KD) (35). In the present study, we examined the role of angiotensin type 1 receptor (AT(1)R) in mediating the effect of K restriction on K secretion. We confirmed the previous finding that K restriction increased the superoxide anion level, c-Src expression, and the phosphorylation of both p38 and extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) in renal cortex and outer medulla. However, the effect of K restriction on superoxide anion generation, c-Src expression, and MAPK phosphorylation was significantly attenuated in rats receiving losartan, an inhibitor of AT(1)R. In contrast, losartan treatment had no effect on superoxide anion level, c-Src expression, and MAPK phosphorylation in animals on a normal K diet (NK). K restriction decreased SK channel activity and increased the tyrosine phosphorylation of ROMK. However, inhibiting AT(1)R abolished the effect of K restriction on SK channels and tyrosine phosphorylation of ROMK channels. The notion that AT(1)R is involved in regulating renal K excretion was also supported by the experiments with metabolic cages showing that losartan treatment significantly enhanced urinary K loss in rats on a KD diet while it had no effect in animals on a NK diet. Consequently, losartan-treated animals had severe hypokalemia in response to K restriction compared with rats without losartan intake. We conclude that AT(1)R is involved in mediating the effect of K restriction on superoxide generation, c-Src, and MAPK and that inhibiting AT(1)R impairs renal ability of K conservation in response to K depletion.
Article: Effect of resveratrol and mixtures of resveratrol and mitomycin C on cancer cells under irradiation.[show abstract] [hide abstract]
ABSTRACT: The radiation-biological effects of resveratrol (Res) alone or with mitomycin C (MMC) were investigated under various conditions in human breast cancer cells (MCF-7). The data of the survival curves obtained in aerated media (acting species: 42% OH, 54% 02*-) showed that Res possesses antitumor activity and also acts as an efficient radical scavenger. This property was extremely enhanced in the presence of MMC. In media saturated with N2O (90% OH, 10% H) Res at low concentrations acted as a radiation-protecting agent, but at higher concentrations its cytostatic effect predominated. At the same time, the MMC-activity was reduced. In anaerobic media, Res demonstrated its radiation-protecting ability, but in mixtures the MMC-ability was reduced in comparison to that of pure MMC due to competition reactions between Res and MMC for the available free radicals. Finally, in a cell suspension containing formate as a specific scavenger for OH and H radicals (pH = 7.4), Res successfully competed for these species and showed antitumor activity. Considering the reaction rate constants of the involved substrates and the implemented concentrations in each medium, the kinetic probability of each survival curve was calculated. Based on these data it was evident that the bifunctional property of Res (acting as radiation protector and also having antitumor activity) was based on an electron ejection process from its excited single state and on its reactivity with the primary radicals (OH, H, e(aq)-).Anticancer research 26(6B):4403-8. · 1.73 Impact Factor
Article: [A round-the-clock information service for malignant hyperthermia emergencies: regional exchange of central information].Der Anaesthesist 12/1987; 36(11):668. · 0.99 Impact Factor