Perspectives in Pharmacology Hypoxia in the Renal Medulla: Implications for Hydrogen Sulfide Signaling

Hydrogen sulfide (H2S) is enzymatically generated in mam-malian tissues from either L-cysteine or L-homocysteine. H2S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide pro-duced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activat-ing ATP-sensitive potassium channels. In addition, H2S pro-duced locally within the kidney stimulates natriuresis and diuresis by increasing glomerular filtration and inhibiting tu-bular sodium reabsorption. Because H2S is oxidized in mi-tochondria in pO2-dependent manner and ambient pO2 is physiologically low in the renal medulla, it is expected that the activity of H2S is higher in the medullary region than the cortical region. H2S, accumulating in increased amounts i