EFFECT OF GENETIC POLYMORPHISMS IN THE EPOXYGENASE PATHWAY ON SALT EXCRETION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Arachidonic acid metabolities generated by the cytochrome P450 pathway, epoxyeicosatrienoic acid (EETs) are known to inhibit renal sodium reaborption in animal models and may have similar effects in healthy human subjects which may be perturbed in salt-sensitive and/or salt-resistent hypertension. Genetic polymorphisms in this P450 Pathway (the epoxygenase pathway) may lead to altered levels of EETs, DHETS and renal salt excretion and may play a mechanistic role in salt-sensitive hypertension. Specific Aim 1: Genotype hypertensive subjects for polymorphisms of the epoxygenase pathway (CYP2J2, CYP2C8, CYP2C9, and sEH) and compare the frequency of variant alleles age and race matched controls in African-American and Caucasian populations. Specific Aim 2: Determine the effect of salt loading and salt depletion on urinary and plasma arachidonic acid metabolites in salt-sensitive (SS) and salt-resistant (SR) hypertension in African-American and Caucasian populations. Specific Aim 3: Determine the effect of epoxygenase genotype on response to salt loading and salt depletion and correlate these effects with plasma and urinary arachidonic acid metabolites in various subgroups in SS and SR hypertension.