β1 receptors protect the renal afferent arteriole of angiotensin-infused rabbits from norepinephrine-induced oxidative stress

Abstract

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 β-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 (β1-receptor agonist; 78 ± 6%; P < 0.0001; mean ± SD) but only weak relaxations to salbutamol (β2-receptor agonist; 13 ± 3%; P < 0.05) or BRL-37,344 (β3-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 (α1 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 β antagonist; -53 ± 6%), CGP-20,712A (selective β1-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 β2-receptor antagonist) or SR-59,230A (selective β3-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 α1-receptor contraction and β1-receptor dilation. NE elicits β1 signaling via cAMP that moderates oxidative stress and contractions in Aff from AngII-infused rabbits. Copyright © 2006 by the American Society of Nephrology.