title: Angiotensin II evokes sensory long-term facilitation of the carotid body via NADPH oxidase.
abstract: We previously reported that reactive oxygen species generated by NADPH oxidase 2 (Nox2) induces sensory plasticity of the carotid body, manifested as a progressive increase in baseline sensory activity or sensory long-term facilitation (sLTF). ANG II, a peptide generated within the carotid body, is a potent activator of Nox2. In the present study, we tested the hypothesis that ANG II evokes sLTF of the carotid body via Nox2 activation. Experiments were performed on carotid bodies ex vivo from adult rats and mice. Sensory activity was recorded from the carotid sinus nerve. Repetitive (5 times for 30 s each at 5-min intervals), but not continuous (for 150 s), application of 60 pM ANG II evoked robust sLTF of the carotid body. ACh, ATP, substance P, and KCl, when applied repetitively, stimulated the carotid body but did not evoke sLTF. Reactive oxygen species levels increased in response to repetitive applications of ANG II, and this effect was blocked by apocynin, an inhibitor of Nox2, as well as losartan, an angiotensin type 1 (AT(1)) receptor antagonist. Losartan, apocynin, and 4-(2-aminoethyl)benzenesulfonyl fluoride prevented ANG II-induced sLTF, which was absent in mice deficient in gp91(phox), the catalytic subunit of the Nox2 complex. These results demonstrate that repetitive application of ANG II induces sLTF of the carotid body via activation of Nox2 by AT(1) receptors.
authors.affiliation: Institute for Integrative Physiology and Center for Systems Biology of O₂ Sensing, Biological Science Division, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Peng
authors.forename: Gayatri
authors.initials: G
authors.lastname: Raghuraman
authors.forename: Shakil A
authors.initials: SA
authors.lastname: Khan
authors.forename: Ganesh K
authors.initials: GK
authors.lastname: Kumar
authors.forename: Nanduri R
authors.initials: NR
authors.lastname: Prabhakar
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002346:Carotid Sinus / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008297:Male; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013995:Time
chemical_list: D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D013373:Substance P; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D019255:NADPH Oxidases; D000109:Acetylcholine