Back to Search
Start Over
Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney
- Source :
- American Journal of Physiology-Renal Physiology. 305:F1680-F1686
- Publication Year :
- 2013
- Publisher :
- American Physiological Society, 2013.
-
Abstract
- We have recently demonstrated that intrarenal dopamine plays an important role in preventing the development of systemic hypertension. Similarly, renal cytochrome P-450 (CYP)-epoxygenase-derived arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), also are antihypertensive through inhibiting sodium reabsorption and vasodilation. The potential interaction between renal dopamine and epoxygenase systems was investigated. Catechol- O-methyl-transferase (COMT)−/−mice with increased intrarenal dopamine levels and proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC−/−) mice with renal dopamine deficiency were treated with a low-salt diet or high-salt diet for 2 wk. Wild-type or Cyp2c44−/−mice were treated with gludopa, which selectively increased renal dopamine levels. In low salt-treated mice, urinary EET levels were related to renal dopamine levels, being highest in COMT−/−mice and lowest in ptAADC−/−mice. In high salt-treated mice, total EET and individual EET levels in both the kidney and urine were also highest in COMT−/−mice and lowest in ptAADC−/−mice. Selective increases in renal dopamine in response to gludopa administration led to marked increases in both total and all individual EET levels in the kidney without any changes in blood levels. qRT-PCR and immunoblotting indicated that gludopa increased renal Cyp2c44 mRNA and protein levels. Gludopa induced marked increases in urine volume and urinary sodium excretion in wild-type mice. In contrast, gludopa did not induce significant increases in urine volume or urinary sodium excretion in Cyp2c44−/−mice. These studies demonstrate that renal EET levels are maintained by intrarenal dopamine, and Cyp2c44-derived EETs play an important role in intrarenal dopamine-induced natriuresis and diuresis.
- Subjects :
- Male
medicine.medical_specialty
Cytochrome
Physiology
Dopamine
Dopamine Agents
Natriuresis
Diuresis
Catechol O-Methyltransferase
Kidney
Cytochrome P-450 CYP2J2
Mice
chemistry.chemical_compound
Cytochrome P-450 Enzyme System
Internal medicine
medicine
Animals
Sodium Chloride, Dietary
Cytochrome P450 Family 2
Cells, Cultured
Mice, Knockout
Aromatic L-amino acid decarboxylase
Arachidonic Acid
Catechol-O-methyl transferase
biology
Articles
Diet, Sodium-Restricted
Dihydroxyphenylalanine
Disease Models, Animal
medicine.anatomical_structure
Endocrinology
chemistry
Aromatic-L-Amino-Acid Decarboxylases
Hypertension
biology.protein
Arachidonic acid
medicine.drug
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 305
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....52a7d98feda8ee4f4910e6fc41a0f83a