Llinás Maria T, Alexander Barbara T, Capparelli Maria F, Carroll Mairead A, Granger Joey P
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505.
Hypertension. 2004 Mar;43(3):623-8. doi: 10.1161/01.HYP.0000117721.83371.9f. Epub 2004 Feb 2.
The present study tested the hypothesis that cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) are involved in mediating hypertension and renal vasoconstriction during chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. 1-aminobenzotriazole (ABT), a CYP enzyme inhibitor (25 mg/kg per day), or vehicle (saline 0.9%) was administered for 7 days to normal pregnant (NP) rats and to pregnant rats with chronic RUPP. RUPP rats infused with vehicle showed significantly (P<0.01) higher mean arterial pressure (MAP) (130+/-2 versus 106+/-1 mm Hg), renal vascular resistance (RVR) (22.6+/-1.8 versus 16.3+/-1.1 mm Hg/mL per minute) and lower (P<0.05) glomerular filtration rate (GFR) (1.6+/-0.1 versus 2.3+/-0.1 mL/min) than NP rats. ABT decreased (P<0.01) MAP in RUPP rats (111+/-1 mm Hg), whereas it had no effect in NP rats (108+/-2 mm Hg). CYP inhibition also attenuated the differences in renal hemodynamics observed between NP and RUPP rats. After treatment with ABT, RVR and GFR were similar in RUPP rats (19.3+/-1.5 mm Hg/mL per minute and 2.0+/-0.2 mL/min, respectively) and NP rats (16.3+/-2.4 mm Hg/mL per minute and 2.4+/-0.2 mL/min). The effects of CYP enzymes inhibitor in RUPP rats were associated with a reduction (P<0.05) of 20-HETE formation (32%) and a decreased (P<0.05) expression (33%) of CYP4A protein in renal cortex. In contrast, renal epoxygenase activity did not change in these animals. These results suggest that 20-HETE contributes to hypertension and renal vasoconstriction induced by chronic RUPP in pregnant rats.
在妊娠大鼠子宫灌注压（RUPP）长期降低期间，花生四烯酸（AA）的细胞色素P - 450（CYP）代谢产物参与介导高血压和肾血管收缩。对正常妊娠（NP）大鼠和患有慢性RUPP的妊娠大鼠给予1 - 氨基苯并三唑（ABT，一种CYP酶抑制剂，每天25 mg/kg）或赋形剂（0.9%生理盐水），持续7天。输注赋形剂的RUPP大鼠的平均动脉压（MAP）显著（P<0.01）更高（130±2对106±1 mmHg），肾血管阻力（RVR）更高（22.6±1.8对16.3±1.1 mmHg/mL每分钟），肾小球滤过率（GFR）更低（P<0.05）（1.6±0.1对2.3±0.1 mL/min），与NP大鼠相比。ABT降低了（P<0.01）RUPP大鼠的MAP（111±1 mmHg），而对NP大鼠无影响（108±2 mmHg）。CYP抑制也减弱了NP大鼠和RUPP大鼠之间观察到的肾血流动力学差异。用ABT治疗后，RUPP大鼠（分别为19.3±1.5 mmHg/mL每分钟和2.0±0.2 mL/min）和NP大鼠（16.3±2.4 mmHg/mL每分钟和2.4±0.2 mL/min）的RVR和GFR相似。CYP酶抑制剂对RUPP大鼠的作用与肾皮质中20 - HETE生成减少（P<0.05）（32%）和CYP4A蛋白表达降低（P<0.05）（33%）有关。相比之下，这些动物的肾环氧合酶活性没有变化。这些结果表明，20 - HETE促成了妊娠大鼠慢性RUPP诱导的高血压和肾血管收缩。
