Regulation of ion transport and blood pressure by cytochrome p450 monooxygenases.
OBJECTIVE
Past and recent studies of the cytochrome P450 monooxygenase branch of the arachidonate cascade establish a role for this metabolic pathway in the regulation of vascular tone and tubular ion transport. Functional and electrophysiology studies indicate that the P450 eicosanoids participate in the regulation of vascular potassium and renal sodium channels, and of systemic blood pressures.


RESULTS
Associations between genetically controlled alterations in blood pressure and the activity or transcriptional regulation of renal Cyp2c arachidonic acid epoxygenases and Cyp4a omega-hydroxylases document a role for these enzymes in the pathophysiology of hypertension--a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. Associations between a functional variant of the human CYP4A11 gene and hypertension suggest a potential role for this gene as a determinant of polygenic blood pressure control in humans.


CONCLUSIONS
These results provide new understandings of the role of P450s in renal physiology, as well as conceptually novel approaches for studies of the molecular basis of human hypertension that could lead to new strategies for the early diagnosis and clinical management of this devastating disease.
Capdevila
Jorge H
JH
Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D001794:Blood Pressure; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000628:therapy; D017136:Ion Transport; D007477:Ions; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D015222:Sodium Channels / Q000737:chemistry
D006893:Hydroxyeicosatetraenoic Acids; D007477:Ions; D015222:Sodium Channels; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D015118:Eicosapentaenoic Acid; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A