title: beta(1) 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 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.
authors.affiliation: Division of Nephrology and Hypertension and the Cardiovascular-Kidney Institute, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Pedro
authors.initials: P
authors.lastname: Jose
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013113:Spin Labels; D013481:Superoxides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D017833:Visceral Afferents / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000975:Antioxidants; D003497:Cyclic N-Oxides; D011943:Receptors, Adrenergic, beta; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D000242:Cyclic AMP; C001803:tempol