Role of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in hypertension.
OBJECTIVE
Cytochrome P-450 metabolites of arachidonic acid have been reported to play an important role in the control of renal function and vascular tone, and in the long-term control of arterial pressure. In this regard, 20-hydroxyeicosatetraenoic acid is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. Epoxyeicosatrienoic acids are endothelium-derived relaxing factors that hyperpolarize vascular smooth muscle cells and also promote sodium excretion in the kidney.


RESULTS
Studies have demonstrated that the expression of cytochrome P-450 enzymes and the synthesis of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in the kidney and peripheral vasculature are altered in many genetic and experimental models of hypertension. The production of these compounds is altered following exposure to high-salt or high-fat diets, in hepatorenal syndrome, in diabetes and in patients with toxemia of pregnancy. However, the functional significance of changes in the formation of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in the pathogenesis of hypertension are just being uncovered.


CONCLUSIONS
This review summarizes recent findings that address the issue of whether cytochrome P-450 metabolites of arachidonic acid play an important role in the regulation of renal tubular and peripheral vascular function and contribute to the pathogenesis of hypertension.
Sarkis
Albert
A
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Lopez
Bernardo
B
Roman
Richard J
RJ
D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D004852:Epoxy Compounds; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000502:physiology*
D001095:Arachidonic Acids; D004852:Epoxy Compounds; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid