title: ANG II signaling in vasa recta pericytes by PKC and reactive oxygen species.
abstract: ANG II constricts descending vasa recta (DVR) through Ca(2+) signaling in pericytes. We examined the role of PKC DVR pericytes isolated from the rat renal outer medulla. The PKC blocker staurosporine (10 microM) eliminated ANG II (10 nM)-induced vasoconstriction, inhibited pericyte cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)) elevation, and blocked Mn(2+) influx into the cytoplasm. Activation of PKC by either 1,2-dioctanoyl-sn-glycerol (10 microM) or phorbol 12,13-dibutyrate (PDBu; 1 microM) induced both vasoconstriction and pericyte [Ca(2+)](cyt) elevation. Diltiazem (10 microM) blocked the ability of PDBu to increase pericyte [Ca(2+)](cyt) and enhance Mn(2+) influx. Both ANG II- and PDBu-induced PKC stimulated DVR generation of reactive oxygen species (ROS), measured by oxidation of dihydroethidium (DHE). The effect of ANG II was only significant when ANG II AT(2) receptors were blocked with PD-123319 (10 nM). PDBu augmentation of DHE oxidation was blocked by either TEMPOL (1 mM) or diphenylene iodonium (10 microM). We conclude that ANG II and PKC activation increases DVR pericyte [Ca(2+)](cyt), divalent ion conductance into the cytoplasm, and ROS generation.
authors.affiliation: Department of Medicine, University of Maryland at Baltimore, Baltimore, MD 21201-1595, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kristie
authors.initials: K
authors.lastname: Rhinehart
authors.forename: Whaseon
authors.initials: W
authors.lastname: Kwon
authors.forename: Edward
authors.initials: E
authors.lastname: Weinman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Pallone
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D009994:Osmolar Concentration; D020286:Pericytes / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium