Abstract
Hydrogen sulfide (H2S) is enzymatically generated in mammalian tissues from either l-cysteine or l-homocysteine. H2S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide produced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activating ATP-sensitive potassium channels. In addition, H2S produced locally within the kidney stimulates natriuresis and diuresis by increasing glomerular filtration and inhibiting tubular sodium reabsorption. Because H2S is oxidized in mitochondria 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 in the renal medulla under hypoxic conditions, may function as an oxygen sensor that restores O2 balance by increasing medullary blood flow, reducing energy requirements for tubular transport, and directly inhibiting mitochondrial respiration. Hypoxia is an important pathogenic factor in many renal diseases, such as ischemia/reperfusion- or nephrotoxin-induced acute renal failure, progression of chronic nephropathies, diabetic nephropathy, and arterial hypertension. Deficiency of endogenous H2S may contribute to the pathogenesis of these pathologies by compromising medullary oxygenation, and administration of H2S donors may be of therapeutic value in these disorders.
Footnotes
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.166637.
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ABBREVIATIONS:
- CSE
- cystathionine |gg-lyase
- CBS
- cystathionine |gb-synthase
- 3-MST
- 3-mercaptopyruvate sulfurtransferase
- CO
- carbon monoxide
- COX-2
- cyclooxygenase-2
- GFR
- glomerular filtration rate
- HIF-1
- hypoxia-induced factor
- HO-1
- heme oxygenase-1
- H2S
- hydrogen sulfide
- KATP
- ATP-sensitive potassium channels
- mTAL
- medullary thick ascending limb
- NCC
- sodium/chloride cotransporter
- NKCC
- sodium/potassium/chloride cotransporter
- NO
- nitric oxide
- SQR
- sulfide/quinone oxidoreductase
- GYY4137
- morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate.
- Received March 17, 2010.
- Accepted April 26, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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