Downregulation of Renal CYP-Derived Eicosanoid Synthesis in Rats With Diet-Induced Hypertension
Autor: | Songbai Lin, Anita Smith, Yiqiang Zhou, John D. Imig, Hsin Hsin Chang, Anne M. Dorrance, Mong Heng Wang, Xueying Zhao |
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Rok vydání: | 2003 |
Předmět: |
Male
Epoxygenase medicine.medical_specialty Down-Regulation Renal function Blood Pressure Biology Kidney Weight Gain urologic and male genital diseases Essential hypertension Cytochrome P-450 CYP2J2 Mixed Function Oxygenases Rats Sprague-Dawley Cytochrome P-450 Enzyme System Internal medicine Internal Medicine medicine Animals Obesity Medulla Arachidonic Acid Microcirculation Cytochrome P450 medicine.disease Diet Rats Endocrinology Blood pressure medicine.anatomical_structure Eicosanoid Hypertension cardiovascular system biology.protein Eicosanoids lipids (amino acids peptides and proteins) Cytochrome P-450 CYP4A |
Zdroj: | Hypertension. 42:594-599 |
ISSN: | 1524-4563 0194-911X |
Popis: | The incidence of essential hypertension increases with obesity; however, the mechanisms that link obesity with hypertension are unclear. Renal cytochrome P450 (CYP)-derived eicosanoids—hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs)—have been shown to play an important role in the regulation of renal function, vascular tone, and blood pressure. The objective of this study was to examine CYP-derived eicosanoid synthesis in the different renal zones (cortex, medulla, and papilla) of rats fed a high fat diet (HF). Male Sprague-Dawley rats were fed a HF diet or regular rat chow for 10 weeks. After 10 weeks, HF rats showed significantly higher systolic blood pressure, body weight, and fat:body weight ratio. The renal ω-hydroxylase activity was decreased by 46% in cortex, 43% in medulla, and 46% in papilla of HF rats. The renal epoxygenase activity was decreased by 46% in cortex, 31% in medulla, and 56% in papilla of HF rats. Interestingly, the changes in the rate of 20-HETE and EET formation in different renal zones were consistent with the levels of expression of CYP4A and CYP2C23 proteins, respectively. Furthermore, there were no significant changes in the synthesis of these metabolites in the renal microvessels. These results demonstrate that HF diet causes the downregulation of CYP4A and CYP2C23 in renal tubules, and these proteins are responsible for renal 20-HETE and EET formation. The reduction in the synthesis of these eicosanoids may play an important role in the regulation of renal function and blood pressure in obesity-induced hypertension. |
Databáze: | OpenAIRE |
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