| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2964216 | Journal of Cardiothoracic-Renal Research | 2006 | 7 Pages |
SummaryIt has been speculated that a reduction in nitric oxide (NO) bioavailability as a result of decreased NO synthase (NOS) cofactor tetrahydrobiopterin (BH4) plays an essential role in cardiovascular pathologies including dilated cardiomyopathy, ischemia–reperfusion injury, endothelial dysfunction, atherosclerosis, hypertension and diabetes. Treatment remedies towards BH4 or its rate-limiting enzyme GTP cyclohydrolase I (GTPCH I) have shown some unusual therapeutic promises against cardiovascular diseases. To the contrary, blockade of BH4 synthesis antagonizes cerebral infarction via inhibition of inducible NOS and ONOO−. In addition, GTPCH I may be stimulated by cytokines including interferon-γ, tumor necrosis factor-α and inflammatory mediators, suggesting a possible role of double-edge sword for BH4 in cardiovascular medicine. Accumulation of free radicals and oxidative stress has been indicated to oxidize BH4, although the precise role of BH4 deficiency in cardiovascular pathophysiology remains largely elusive. Recent pharmacological, gene transfer and transgenic studies have provided new insight towards the ultimate understanding of BH4 in the pathogenesis and therapy of cardiovascular diseases. However, whether BH4 should be considered as a panacea for NO deficiency is debatable. This review intends to update the picture of pathophysiology of BH4 deficiency, pros and cons in therapeutics using BH4 and its rate limiting enzyme GTP cyclohydrolase I (GTPCH I) against NO deficiency.
