title: Nitric oxide at the CVLM is involved in the attenuation of the reflex bradycardia in renovascular hypertensive rats.
abstract: Hypertension is associated to an increase in central oxidative stress and an attenuation of the baroreflex control of arterial pressure. The present study evaluated the effect of alterations in the levels of nitric oxide (NO) and superoxide anion in the caudal ventrolateral medulla (CVLM), a key area of the brainstem for the baroreflex control of arterial pressure, in renovascular hypertensive rats (2K1C). Baseline mean arterial pressure (MAP), heart rate (HR), and reflex bradycardia were evaluated 30 days after renal artery occlusion in anesthetized (urethane, 1.2 g/kg, i.p.) 2K1C or normotensive (SHAM) rats. The MAP, HR, and baroreflex control of HR were evaluated before and after CVLM microinjections of the non-selective NOS inhibitor L-NAME (10 nmol), the NO precursor L-ARG (50 nmol), or the antioxidant ascorbic acid, Vit C (10 nmol). In both 2K1C and SHAM animals, CVLM microinjection of L-NAME produced a decrease in MAP, whereas L-ARG induced a significant increase in MAP. However, microinjection of Vit C into the CVLM produced a decrease in MAP and HR only in 2K1C and not in SHAM rats. Cardiovascular effects produced by microinjection of l-ARG into the CVLM were abolished by prior microinjection of L-NAME in the CVLM of 2K1C and SHAM rats. Microinjection of L-NAME into the CVLM increased the sensitivity of reflex bradycardia in 2K1C animals. In contrast, the CVLM microinjection of L-ARG reduced reflex bradycardia only in SHAM rats. Vit C in the CVLM did not change reflex bradycardia in either 2K1C or in SHAM rats. These results suggest that increased oxidative stress in the CVLM during hypertension contributes to the reduced baroreflex sensitivity and to maintain hypertension in the 2K1C model.
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
authors.forename: Uberdan Guilherme Mendes
authors.initials: UG
authors.lastname: de Castro
authors.forename: Graziele Galdino
authors.initials: GG
authors.lastname: de Sousa
authors.forename: Raquel do Pilar
authors.initials: Rdo P
authors.lastname: Machado
authors.forename: Mauro César
authors.initials: MC
authors.lastname: Isoldi
authors.forename: Marcelo Eustáquio
authors.initials: ME
authors.lastname: Silva
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Nadu
authors.forename: Luiz Eduardo
authors.initials: LE
authors.lastname: Sousa
authors.forename: Robson Augusto Souza Dos
authors.initials: RA
authors.lastname: Santos
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Campagnole-Santos
authors.forename: Andréia Carvalho
authors.initials: AC
authors.lastname: Alzamora
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester