title: Renal vasoconstriction by vasopressin V1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38.
abstract: Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38(-/-) mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3-25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38(-/-) mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38(-/-) mice. Inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38(-/-) (P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38(-/-) mice (P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains (P < 0.005) but was ineffective when administered after L-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by L-NAME and indomethacin (P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways.
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina nmoss@email.unc.edu.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Moss
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Tayler E
authors.initials: TE
authors.lastname: Kopple
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: William J
authors.initials: WJ
authors.lastname: Arendshorst
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D003497:Cyclic N-Oxides; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D017483:Receptors, Vasopressin; D013113:Spin Labels; D013481:Superoxides; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D051997:ADP-ribosyl Cyclase 1; C001803:tempol
keywords: V1a receptor; arginine vasopressin; indomethacin; nitro-l-arginine methyl ester; prostaglandin E2; prostaglandin I2; reactive oxygen species; renal blood flow; renal vascular resistance; superoxide dismutase; tempol