AFLUID May 45/5

Good, David W., Thampi George, and Donna H. Wang. Angiotensin II inhibits HCO3 2 absorption via a cytochrome P-450-dependent pathway in MTAL. Am. J. Physiol. 276 (Renal Physiol. 45): F726–F736, 1999.—The role of ANG II in the regulation of ion reabsorption by the renal thick ascending limb is poorly understood. Here, we demonstrate that ANG II (1028 M in the bath) inhibits HCO3 2 absorption by 40% in the isolated, perfused medullary thick ascending limb (MTAL) of the rat. The inhibition by ANG II was abolished by pretreatment with eicosatetraynoic acid (10 μM), a general inhibitor of arachidonic acid metabolism, or 17-octadecynoic acid (10 μM), a highly selective inhibitor of cytochrome P-450 pathways. Bath addition of 20-hydroxyeicosatetraenoic acid (20-HETE; 1028 M), the major P-450 metabolite in the MTAL, inhibited HCO3 2 absorption, whereas pretreatment with 20HETE prevented the inhibition by ANG II. The addition of 15-HETE (1028 M) to the bath had no effect on HCO3 2