Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced byl -NAME treatment in pregnant rats
| Autor: | Yiqiang Zhou, Michael W. Brands, Cong-Yi Wang, John R. Falck, Juan Du, Venugopal T. Raju, Mong Heng Wang, Hui Huang, Hsin Hsin Chang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Kidney Cortex Physiology Urinary system Hemodynamics Blood Pressure Nitric Oxide Nitric oxide chemistry.chemical_compound Pregnancy Internal medicine Hydroxyeicosatetraenoic Acids medicine Animals Sulfones Kidney business.industry Age Factors medicine.disease Amides Rats NG-Nitroarginine Methyl Ester medicine.anatomical_structure Endocrinology chemistry Eicosanoid Regional Blood Flow Pregnancy Animal Gestation Female Arachidonic acid business |
| Zdroj: | American Journal of Physiology-Renal Physiology. 289:F1116-F1122 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | We previously reported that inhibition of nitric oxide (NO) synthesis by N-nitro-l-arginine methyl ester (l-NAME) during late pregnancy leads to increased production of renal vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 (CYP) 4A-derived vasoconstrictor, in pregnant rats. However, the effect of upregulation of vascular 20-HETE production on renal function after NO inhibition is not known. To test the hypothesis that increased gestational vascular 20-HETE synthesis after NO inhibition is involved in mediating blood pressure and renal functional changes, we first determined the IC50value of the effect of nitroprusside (SNP), a NO donor, on renal 20-HETE production in cortical microsomes. We then divided pregnant rats and age-matched virgin rats into a vehicle control group, an l-NAME treatment group (0.25 mg/ml in drinking water), and a group treated with l-NAME plus N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; CYP4A-selective inhibitor, 10 mg·kg−1·day−1iv). After 4 days of treatment, we measured blood pressure, renal blood flow (RBF), renal vascular resistance (RVR), and glomerular filtration rate (GFR) in each group. The addition of SNP (IC50= 22 μM) decreased renal cortical 20-HETE production. In pregnant rats, l-NAME treatment led to significantly higher mean arterial pressure (MAP) and RVR, and lower RBF and GFR. Combined treatment with DDMS and l-NAME significantly attenuated the increases in MAP and RVR and the decrease in GFR, but not the reduction in RBF induced by l-NAME treatment. l-NAME and l-NAME plus DDMS had no significant impact on renal hemodynamics in virgin rats. In addition, chronic treatment with DDMS selectively inhibited cortical 20-HETE production without a significant effect on CYP4A expression in l-NAME-treated pregnant rats. In conclusion, NO effectively inhibits renal cortical microsomal 20-HETE production in female rats. In pregnant rats, the augmentation of renal 20-HETE production after NO inhibition is associated with increased MAP and RVR, whereas decreased GFR is negated by treatment of a selective and competitive CYP4A inhibitor. These results demonstrate that the interaction between renal 20-HETE and NO is important in the regulation of renal function and blood pressure in pregnant rats. |
| Databáze: | OpenAIRE |
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