Rajapakse Niwanthi W, Eppel Gabriela A, Widdop Robert E, Evans Roger G
Department of Physiology, Monash University, Melbourne 3800, Victoria, Australia.
Am J Physiol Regul Integr Comp Physiol. 2006 Dec;291(6):R1669-76. doi: 10.1152/ajpregu.00183.2006. Epub 2006 Jul 20.
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.
外源性和内源性血管紧张素II（ANG II）激活血管紧张素2型（AT(2)）受体，可调节肾皮质和髓质循环中神经介导的血管收缩。在戊巴比妥麻醉的家兔的对照条件下，电刺激肾神经（RNS；0.5 - 8 Hz）对肾血流量（RBF；8 Hz时为-88 ± 3%）和皮质灌注（CBF；8 Hz时为-92 ± 2%）的减少作用大于对髓质灌注（MBF；8 Hz时为-67 ± 6%）。以能使RBF降低约40 - 50%（5 - 50 ng·kg(-1)·min(-1)）的剂量经肾动脉输注ANG II，可减弱MBF对RNS的反应，而对RBF或CBF的反应无显著影响。在持续经肾动脉输注ANG II期间，随后给予PD123319（1 mg/kg加1 mg·kg(-1)·h(-1)）对RBF或CBF对RNS的反应无显著影响，但增强了MBF的反应，使其与对照条件下观察到的反应相似。相反，单独给予PD123319可减弱CBF和MBF对RNS的反应。在预先用PD123319处理的家兔中随后经肾动脉输注ANG II，可使CBF对RNS的反应恢复到对照水平。相反，在预先用PD123319处理的家兔中输注ANG II不会改变MBF对RNS的反应。这些数据表明，外源性ANG II可通过激活AT(2)受体减弱髓质循环中神经介导的血管收缩。然而，内源性ANG II激活AT(2)受体似乎可增强皮质和髓质循环中神经介导的血管收缩。
