Detroit R & D, Inc.

University of California

Other

Deanna Kroetz

Hyesook Kim

Jorge H Capdevila

Raymond R Novak

Bruce D Hammock

Christophe H Morisseau

Darryl C Zeldin

Raymond F Novak

A method of assessing arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA). An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs.

Detection of hypertension using glucuronidated metabolic products

A method to assess arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA) is disclosed. An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs. The present invention measuring glucuronidated DHET levels in a biological sample is useful for drug development and monitoring efficiency of drug treatment of a mammal who has AA epoxygenase-, epoxide hydrolase-and/or UDP-glucuronosyl transferase-dependent hypertension.

Inhibitors of epoxide hydrolases for the treatment of hypertension

A method to assess hypertension by measuring the amount of free and conjugated hydroxyeicosatrienoic acids (DHETs) and metabolites of DHETs, which are metabolites of arachidonic acid (AA) epoxygenases and epoxide hydrolases, in a biological sample which contains the DHETs (using any methods including GC/MS or ELISA) is disclosed. The method further included determining the amount of molecules containing a DHET-specific epitope immunoreactive with antibodies produced against DHETs present in the sample. This amount is compared with a control sample(s). Hypertension is determined through the comparison wherein the amount of increase of free and conjugated DHETs and metabolites of DHETs in the sample isolated from an organism. The present invention also provides a method to assess catalytic activity of AA epoxygenases using immunoassays by subtracting the amounts of NADPH-independent epoxyeicosatriencic acids (EETs) from total (NADPH-dependent&plus;independent) EETs. The present invention also provides a method to decrease hepatic M epoxygenase expression including 2C23 by treatment of rats with a glucocorticoid including dexamethasone.

Detection of hypertension using immunoreactive metabolic products

A method to assess hypertension by measuring the amount of free and conjugated hydroxyeicosatrienoic acids (DHETS) and metabolites of DHETs, which are metabolites of arachidonic acid (AA) epoxygenases and epoxide hydrolases, in a biological sample which contains the DHETs (using any methods including GC/MS or ELISA) is disclosed. The method further included determining the amount of molecules containing a DHET-specific epitope immunoreactive with antibodies produced against DHETs present in the sample. This amount is compared with a control sample(s). Hypertension is determined through the comparison wherein the amount of increase of free and conjugated DHETs and metabolites of DHETs in the sample isolated from an organism. The present invention also provides a method to assess catalytic activity of AA epoxygenases using immunoassays by measuring the amounts of NADPH-independent epoxyeicosatrienoic acids (EETs) and total (NADPH-dependent&plus;independent) EETs. The present invention also provides a method to decrease hepatic AA epoxygenase expression including 2C23 by treatment of rats with a glucocorticoid including dexamethasone.

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San Francisco, CA, United States of America

Deanna Kroetz