Search

We tested the hypothesis that activation of angiotensin type 2 (AT2) 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 ∼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 AT2 receptors. However, AT2-receptor activation by endogenous ANG II appears to enhance neurally mediated vasoconstriction in both the cortical and medullary circulations.

We investigated the roles of the renin-angiotensin system and the significance of interactions between angiotensin II and nitric oxide, in responses of regional kidney perfusion to electrical renal nerve stimulation (RNS) in pentobarbital sodium-anesthetized rabbits. Under control conditions, RNS (0.5–8 Hz) reduced total renal blood flow (RBF; −89 ± 3% at 8 Hz) and cortical perfusion (CBF; −90 ± 2% at 8 Hz) more than medullary perfusion (MBF; −55 ± 5% at 8 Hz). Angiotensin II type 1 (AT1)-receptor antagonism (candesartan) blunted RNS-induced reductions in RBF ( P = 0.03), CBF ( P = 0.007), and MBF ( P = 0.04), particularly at 4 and 8 Hz. Nitric oxide synthase inhibition with NG-nitro-l-arginine (l-NNA) enhanced RBF ( P = 0.003), CBF ( P = 0.001), and MBF ( P = 0.03) responses to RNS, particularly at frequencies of 2 Hz and less. After candesartan pretreatment, l-NNA significantly enhanced RNS-induced reductions in RBF ( P = 0.04) and CBF ( P = 0.007) but not MBF ( P = 0.66). Renal arterial infusion of angiotensin II (5 ng·kg−1·min−1) selectively enhanced responses of MBF to RNS in l-NNA-pretreated but not in vehicle-pretreated rabbits. In contrast, greater doses of angiotensin II (5–15 ng·kg−1·min−1) blunted responses of MBF to RNS in rabbits with intact nitric oxide synthase. These results suggest that endogenous angiotensin II enhances, whereas nitric oxide blunts, neurally mediated vasoconstriction in the renal cortical and medullary circulations. In the renal medulla, but not the cortex, angiotensin II also appears to be able to blunt neurally mediated vasoconstriction.