Role of chloride in constriction of descending vasa recta by angiotensin II

We investigated the dependence of ANG II (10(-8) M)-induced constriction of outer medullary descending vasa recta (OMDVR) on membrane potential (Cm) a nd chloride ion. ANG II depolarized OMDVR, as measured by fully loading the m with the voltage-sensitive dye bis[1,3-dibutylbarbituric acid-(5)] trimet hineoxonol [DiBAC(4)(3)] or selectively loading their pericytes. ANG II was also observed to depolarize pericytes from a resting value of -55.6 +/- 2. 6 to -26.2 +/- 5.4 mV when measured with gramicidin D-perforated patches. W hen measured with DiBAC4(3) in unstimulated vessels, neither changing extra cellular Cl- concentration ([Cl-]) nor exposure to the chloride channel blo cker indanyloxyacetic acid 94 (IAA-94; 30 muM) affected Psim. In contrast, IAA-94 repolarized OMDVR pretreated with ANG II. Neither IAA-94 (30 muM) no r niflumic acid (30 muM, 1 mM) affected the vasoactivity of unstimulated OM DVR, whereas both dilated ANG II-preconstricted vessels. Reduction of extra cellular [Cl-] from 150 to 30 meq/l enhanced ANG II-induced constriction. F inally, we identified a Cl- channel in OMDVR pericytes that is activated by ANG II or by excision into extracellular buffer. We conclude that constric tion of OMDVR by ANG II involves pericyte depolarization due, in part, to i ncreased activity of chloride channels.