ANG II type 2 receptors and neural control of intrarenal blood flow.
We tested the hypothesis that activation of angiotensin type 2 (AT(2)) receptors, by both exogenous and endogenous ANG II, modulates neurally mediated vasoconstriction in the renal cortical and medullary circulations. Under control conditions in pentobarbital-anesthetized rabbits, electrical stimulation of the renal nerves (RNS; 0.5-8 Hz) reduced renal blood flow (RBF; -88 +/- 3% at 8 Hz) and cortical perfusion (CBF; -92 +/- 2% at 8 Hz) more than medullary perfusion (MBF; -67 +/- 6% at 8 Hz). Renal arterial infusion of ANG II, at a dose titrated to reduce RBF by approximately 40-50% (5-50 ng.kg(-1).min(-1)) blunted responses of MBF to RNS, without significantly affecting responses of RBF or CBF. Subsequent administration of PD123319 (1 mg/kg plus 1 mg.kg(-1).h(-1)) during continued renal arterial infusion of ANG II did not significantly affect responses of RBF or CBF to RNS but enhanced responses of MBF, so that they were similar to those observed under control conditions. In contrast, administration of PD123319 alone blunted responses of CBF and MBF to RNS. Subsequent renal arterial infusion of ANG II in PD123319-pretreated rabbits restored CBF responses to RNS back to control levels. In contrast, ANG II infusion in PD123319-pretreated rabbits did not alter MBF responses to RNS. These data indicate that exogenous ANG II can blunt neurally mediated vasoconstriction in the medullary circulation through activation of AT(2) receptors. However, AT(2)-receptor activation by endogenous ANG II appears to enhance neurally mediated vasoconstriction in both the cortical and medullary circulations.
Rajapakse
Niwanthi W
NW
Department of Physiology, Monash University, Melbourne 3800, Victoria, Australia.
Eppel
Gabriela A
GA
Widdop
Robert E
RE
Evans
Roger G
RG
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation*; D008297:Male; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II