Inhibition of calcium signaling in descending vasa recta endothelia by ANG II

The intracellular calcium ([Ca2+](i)) response of outer medullary descending vasa recta (OMDVR) endothelia to ANG II was examined in fura 2-loaded vessels. Abluminal ANG II (10(-8) M) caused [Ca2+](i) to fall in proportion to the resting [Ca2+](i) (r = 0.82) of the endothelium. ANC II (10(-8) M) also inhibited both phases of the [Ca2+](i) response generated by bradykinin (BK, 10(-7) M), 835 +/- 201 versus 159 +/- 30 nM (peak phase) and 169 +/- 26 versus 103 +/- 14 nM (plateau phase) (means i SE). Luminal ANG II reduced BK (10(-7) M)-stimulated plateau [Ca2+](i) from 180 +/- 40 to 134 +/- 22 nM without causing vasoconstriction. Abluminal ANG II added to the bath after luminal application further reduced [Ca2+](i) to 113 +/- 9 nM and constricted the vessels. After thapsigargin (TG) pretreatment, ANG II (10-8 M) caused [Ca2+](i) to fall from 352 +/- 149 to 105 +/- 37 nM. This effect occurred at a threshold ANG II concentration of 10(-10) M and was maximal at 10(-8) M. ANG II inhibited both the rate of Ca2+ entry into [Ca2+](i)-depleted endothelia and the rate of Mn2+ entry into [Ca2+](i)-replete endothelia. In contrast, ANG II raised [Ca2+](i) in the medullary thick ascending limb and outer medullary collecting duct, increasing [Ca2+](i) from baselines of 99 +/- 33 and 53 +/- 11 to peaks of 200 +/- 47 and 65 +/- 11 nM, respectively. We conclude that OMDVR endothelia are unlikely to be the source ofANG II-stimulated NO production in the medulla but that interbundle nephrons might release Ca2+-dependent vasodilators to modulate vasomotor tone in vascular bundles.