Wang Dan, Jose Pedro, Wilcox Christopher S
Division of Nephrology and Hypertension and the Cardiovascular-Kidney Institute, Georgetown University Medical Center, Washington, DC 20007, USA.
J Am Soc Nephrol. 2006 Dec;17(12):3347-54. doi: 10.1681/ASN.2006030212. Epub 2006 Nov 15.
Renal afferent arterioles (Aff) from angiotensin II (AngII)-infused rabbits have enhanced contractions to AngII that are normalized by tempol (superoxide dismutase mimetic), whereas contractions to norepinephrine (NE) are normal and unaffected by tempol. Tested was the hypothesis that beta-receptor stimulation with NE prevents enhanced reactivity and superoxide generation. Preconstricted Aff from AngII- or vehicle-infused rabbits were perfused at physiologic pressure. Aff from vehicle-infused rabbits had strong, endothelium-independent relaxations to dobutamine (beta(1)-receptor agonist; 78 +/- 6%; P < 0.0001; mean +/- SD) but only weak relaxations to salbutamol (beta(2)-receptor agonist; 13 +/- 3%; P < 0.05) or BRL-37,344 (beta(3)-receptor agonist; 14 +/- 3%; P < 0.05). Contractions to NE were similar in Aff from vehicle- and AngII-infused rabbits (-36 +/- 5 versus -34 +/- 3%; NS) and were unaffected by tempol (-32 +/- 4%; NS). In contrast, phenylephrine contractions (alpha(1) agonist) were enhanced in Aff from AngII-infused rabbits (-59 +/- 6 versus -46 +/- 4%; P < 0.05) and normalized by tempol. NE contractions in Aff from AngII-infused rabbits (-34 +/- 4%) were enhanced (P < 0.01) by propranolol (nonselective beta antagonist; -53 +/- 6%), CGP-20,712A (selective beta(1)-receptor antagonist; -61 +/- 9%), or Rp-cAMP (competitive inhibitor of cAMP; -56 +/- 4%); were normalized by tempol; but were unaffected by ICI-118,551 (selective beta(2)-receptor antagonist) or SR-59,230A (selective beta(3)-receptor antagonist). Superoxide generation in Aff from AngII-infused rabbits that were assessed from ethidium:dihydroethidium was enhanced by addition of CGP-20,712A to NE but was normalized by tempol. Aff have robust alpha(1)-receptor contraction and beta(1)-receptor dilation. NE elicits beta(1) signaling via cAMP that moderates oxidative stress and contractions in Aff from AngII-infused rabbits.
来自输注血管紧张素II（AngII）的兔子的肾入球小动脉（Aff）对AngII的收缩增强，而tempol（超氧化物歧化酶模拟物）可使其恢复正常，而对去甲肾上腺素（NE）的收缩正常且不受tempol影响。检验的假设是，用NE刺激β受体可防止反应性增强和超氧化物生成。将来自输注AngII或赋形剂的兔子的预收缩Aff在生理压力下灌注。来自输注赋形剂的兔子的Aff对多巴酚丁胺（β1受体激动剂；78±6%；P<0.0001；平均值±标准差）有强烈的、不依赖内皮的舒张作用，但对沙丁胺醇（β2受体激动剂；13±3%；P<0.05）或BRL-37,344（β3受体激动剂；14±3%；P<0.05）只有微弱的舒张作用。在来自输注赋形剂和AngII的兔子的Aff中，对NE的收缩相似（-36±5%对-34±3%；无显著性差异），且不受tempol影响（-32±4%；无显著性差异）。相比之下，苯肾上腺素收缩（α1激动剂）在来自输注AngII的兔子的Aff中增强（-59±6%对-46±4%；P<0.05），并被tempol恢复正常。在来自输注AngII的兔子的Aff中，NE收缩（-34±4%）被普萘洛尔（非选择性β拮抗剂；-53±6%）、CGP-20,712A（选择性β1受体拮抗剂；-61±9%）或Rp-cAMP（cAMP竞争性抑制剂；-56±4%）增强（P<0.01）；被tempol恢复正常；但不受ICI-118,551（选择性β2受体拮抗剂）或SR-59,230A（选择性β3受体拮抗剂）影响。通过乙锭：二氢乙锭评估，在来自输注AngII的兔子的Aff中，添加CGP-20,712A到NE可增强超氧化物生成，但被tempol恢复正常。Aff具有强大的α1受体收缩和β1受体舒张作用。NE通过cAMP引发β1信号，从而减轻来自输注AngII的兔子的Aff中的氧化应激和收缩。
