factor

It is well-known that the endothelium plays an important role in the regulation of vascular tone by synthesis and release of endothelium-derived relaxing factors (EDRFs), including NO, prostacyclin ([PCI.sub.2]) and EDHF (Luscher 1990).

Cytochrome P450 2C is an EDHF synthase in coronary arteries.

In coronary arteries, estrogens stimulate the release of three distinct endothelium-derived relaxation compounds: NO, [PGI.sub.2] and EDHF. Our previous studies have revealed the relationships between estrogens and these endothelium-derived factors in the coronary vascular bed in normotensive (6) as well as in hypertensive rats (22).

It is likely that contribution by the variable EDRF such as NO, prostacyclin, and EDHF caused vascular smooth muscle cells to relax.

This was surprising because one would have expected carriers of CYP2C9 mutant alleles to exhibit reduced CYP2C9 metabolic capacity, leading to decreased endothelial EDHF synthesis and an increased risk for MI.

There is evidence suggesting that additional mechanisms are involved in endothelial control of vascular tone, such as prostacyclins (33,34) and endothelium-derived hyperpolarizing factor (EDHF), a cytochrome P450-derived arachidonic acid metabolite (35-37).

Vasodilation effects of EOFAZ were totally abolished by mechanical removal of the endothelium, suggesting that they are dependent upon released endothelium-derived relaxant factors such as nitric oxide (NO), PGI2 and/or endothelium-derived hyperpolarizing factor (EDHF).

This effect was associated with a marked reduction of the endothelium-derived hyperpolarizing factor (EDHF) component whereas the nitric oxide (NO) component was not affected.

2006), while P2[X.sub.1] receptor mediates a small vasoconstriction, followed by a profound and sustained endothelium-dependent vasodilatation, acting through EDHF rather than prostacyclin or NO (Harrington and Mitchell 2004).

In addition, [PGI.sub.2], EDHF and CO pathways also partially participated in vasodilation induced by TGS.