title: Superoxide scavenging in the rostral ventrolateral medulla blunts the pressor response to peripheral chemoreflex activation.
abstract: Peripheral chemoreflex activation has been considered the key drive for the overactivity of the sympathetic nervous system observed in some pathological conditions such as sleep obstructive apnea. In addition, increases in angiotensin-II-derived reactive oxygen species found in some autonomic regulatory brain areas have been implicated in hypertension. However, a link between oxidative stress and peripheral chemoreflex integration within the RVLM has never been investigated. Here, we tested the hypothesis that the pressor response induced by peripheral chemoreflex activation involves the angiotensin-II/AT(1)R/superoxide pathway within the rostral ventrolateral medulla (RVLM). Seventeen male Wistar rats (260-300 g) were implanted with bilateral guide cannulae towards the RVLM and were fitted with catheters for blood pressure recordings and drug administration. Peripheral chemoreflex activation with potassium cyanide (80 microg/kg, i.v.) produced a transient increase in blood pressure, which was attenuated 2 minutes after bilateral microinjection of losartan (1 nmol), an AT(1) receptor antagonist, in the RVLM (+54+/-4 vs +19+/-3 Delta mmHg, P<0.05, n=6). Moreover, superoxide scavenging in the RVLM using a superoxide dismutase (SOD) mimetic, Tempol (5 nmol), significantly blunted the pressor response to peripheral chemoreflex activation (+50+/-3 vs +18+/-3 Delta mmHg, P<0.05, n=7). On the other hand, bilateral microinjection of saline (n=4) in the RVLM produced no change in the pressor response to chemoreflex activation. Taken together, these data suggest that the neurotransmission of the peripheral chemoreflex within the RVLM involves, at least in part, the activation of AT(1) receptors and downstream superoxide formation.
authors.affiliation: Department of Veterinary Sciences, Federal University of Paraíba, Areia, PB, Brazil, 58397-000.
authors.forename: Fabíola C
authors.initials: FC
authors.lastname: Nunes
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, PB, Brazil, 58.051-970.
authors.forename: Thaís P
authors.initials: TP
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, PB, Brazil, 58.051-970.
authors.forename: Maria S
authors.initials: MS
authors.lastname: França-Silva
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, PB, Brazil, 58.051-970.
authors.forename: Isac A
authors.initials: IA
authors.lastname: Medeiros
authors.affiliation: Department of Veterinary Sciences, Federal University of Paraíba, Areia, PB, Brazil, 58397-000; Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, PB, Brazil, 58.051-970. Electronic address: valdir@ltf.ufpb.br.
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Braga
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D011311:Pressoreceptors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D013481:Superoxides; D011190:Potassium Cyanide