Molecular mechanism on the maturation of tissue oxygen supply system

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Maturation of tissue oxygen supply system is an important issue to supply oxygen to tissues after tissue injury or vascular obstruction. Sphingosine 1-Phosphate, S1P is a lipid mediator derived from platelets and is supposed to be involved in the angiogenesis and its maturation through its G-protein-coupled S1P1 receptor. We examined whether ROS affects S1P1 receptor expression. The results suggest ROS seems to be involved, however, we must now resolve the induction mechanism. The other studies concerning ROS and pathophysiologic state we did is as follows ; We detected that high salt loading for 4 weeks increased excretion of H_2O_2 in urine of Dahl salt sensitive rats, NADPH-dependent superoxide producing activity in enal cortex, urinary 8-isoprostane and thromboxane B_2 excretion, and decreased plasma NO end products, which were counteracted by L-arginine supplement. We examined an increase in the expressions of NADPH oxidase subunits, gp91phox and p47phox, mRNA abundance with RT-PCR in renal cortex, which was counteracted with oral L-arginine supplement. Western blot revealed that high-salt loading increased gp9lphox protein, which was counteracted by L-arginine supplement both in the total homogenates and in the membrane fractions. High-salt loading powerfully increased p47phox protein, which was distinctly counteracted by L-arginine supplement only in the membrane fractions. These results disclosed that high salt loading causes a deficiency in available L-arginine for NO sythases and induces NADPH oxidase activation in the renal cortex of DS rats, which were counteracted by L-arginine supplement. Superoxide production in the renal cortex of DS rats will accelerate sodium reabsorption and hypertension, since NO inhibits sodium reabsorption in the cortical collecting duct and superoxide rapidly eliminates NO.