Imig J D, Zou A P, Ortiz de Montellano P R, Sui Z, Roman R J
Department of Physiology, Medical College of Wisconsin, Milwaukee.
Am J Physiol. 1994 May;266(5 Pt 2):H1879-85. doi: 10.1152/ajpheart.1994.266.5.H1879.
The present study evaluated the effects of cytochrome P-450 inhibitors on the response of the renal microvasculature to changes in renal perfusion pressure and on autoregulation of glomerular capillary pressure using the rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free perfusate containing 5% albumin. The basal diameters of the proximal and distal afferent arterioles averaged 28 +/- 1 (n = 32) and 18 +/- 1 micron (n = 23), respectively, at a control perfusion pressure of 80 mmHg. The diameters of these vessels decreased by 8% when perfusion pressure was elevated from 80 to 160 mmHg. After addition of cytochrome P-450 inhibitors (either 17-octadecynoic acid, 20 microM; 7-ethoxyresorufin, 10 microM; or miconazole, 20 microM) to the perfusate, the diameters of the proximal and distal afferent arterioles increased by 6% in response to the same elevation in perfusion pressure. Control glomerular capillary pressure averaged 43 +/- 1 mmHg (n = 32) at a renal perfusion pressure of 80 mmHg and increased by only 9 +/- 1 mmHg when perfusion pressure was elevated to 160 mmHg. Autoregulation of glomerular capillary pressure was impaired after addition of the cytochrome P-450 inhibitors, and it increased by 18 +/- 2 mmHg when perfusion pressure was varied over the same range. These results indicate that cytochrome P-450 inhibitors attenuate the vasoconstrictor response of afferent arterioles to elevations in renal perfusion pressure and impair autoregulation of glomerular capillary pressure, suggesting a possible role for cytochrome P-450 metabolites of arachidonic acid in these responses.
本研究使用体外灌注含5%白蛋白无细胞灌注液的大鼠近髓肾单位微血管制备物，评估细胞色素P - 450抑制剂对肾微血管对肾灌注压变化的反应以及对肾小球毛细血管压力自身调节的影响。在80 mmHg的对照灌注压下，近端和远端传入小动脉的基础直径分别平均为28±1微米（n = 32）和18±1微米（n = 23）。当灌注压从80 mmHg升高到160 mmHg时，这些血管的直径减小了8%。在向灌注液中添加细胞色素P - 450抑制剂（17 - 十八碳炔酸，20微摩尔；7 - 乙氧基试卤灵，10微摩尔；或咪康唑，20微摩尔）后，近端和远端传入小动脉的直径在灌注压同样升高时增加了6%。在80 mmHg的肾灌注压下，对照肾小球毛细血管压力平均为43±1 mmHg（n = 32），当灌注压升高到160 mmHg时仅增加了9±1 mmHg。添加细胞色素P - 450抑制剂后，肾小球毛细血管压力的自身调节受损，当灌注压在相同范围内变化时，其增加了18±2 mmHg。这些结果表明，细胞色素P - 450抑制剂减弱了传入小动脉对肾灌注压升高的血管收缩反应，并损害了肾小球毛细血管压力的自身调节，提示花生四烯酸的细胞色素P - 450代谢产物在这些反应中可能起作用。
