Efeito do Óxido Nítrico na Regulação de Parâmetros Cardiovasculares pela CVLM em Ratos com Hipertensão Renovascular 2R1C / Efeito do Óxido Nítrico na Regulação de Parâmetros Cardiovasculares pela CVLM em Ratos com Hipertensão Renovascular 2R1C

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

28/05/2010

RESUMO

Hypertension may occur due to hyperactivity of neurons in the rostral ventrolateral medulla (RVLM) (Chan et al. 1991; Boone and McMillen, 1994, Suzuki et al. 1994; Minson et al., 1996) and/or due to a reduced tone of GABAergic neurons of the caudal ventrolateral medulla (CVLM) that projects to the RVLM. Furthermore, during hypertension occurs an elevation of nitric oxide (NO) in the CVLM. However, there are no conclusive studies about the role of NO in the CVLM during development and/or maintenance of this pathology. Thus, the objective of this study was to evaluate the effect of NO in the CVLM on the mean arterial pressure (MAP), heart rate (HR) and reflex bradycardia in renovascular hypertensive rats (2K1C). Male Fisher rats (150 to 200g) were anesthetized with a mixture of ketamine (50 mg / kg, ip) and xylazine (5 mg / kg, ip) for the 2K1C or SHAM surgeries. 30 days after these surgeries, the 2K1C and SHAM animals were anesthetized with urethane (1.2 g / kg, ip), positioned in a stereotactic apparatus to expose the medulla and instrumented for MAP and HR measurements. Baroreflex control of HR was determined by recording reflex heart rate changes in response to transient increases in MAP produced by repeated bolus injections of graded doses of phenylephrine (0.25 to 5 mg, iv) before and after microinjections of L-NAME (10nmol) or L-ARGININE (50nmol). After carrying out the experiments the animals were sacrificed. The kidneys and heart were weighed and the brain submitted to histological analysis. The 2K1C animals showed lower relative weight of the left kidney (clipped) (0.28 0.02 g, n=11), increased relative weight of the contralateral kidney (0.52 0.05 g, n=11), greater relative heart weight (0.41 0.02 g, n=11) and left ventricle (0.31 0.02, n=11) and an increase in MAP (142 3 mmHg, n = 36) compared to the SHAM rats (0.34 0.01 g, 0.35 0.01 g, 0.30 0.01 g, 0.20 0.01 g, n = 11 and 106 2 mmHg, n=42 respectively) The microinjection of L-NAME in the CVLM produced a fall in MAP and HR of both animals 2K1C (-17 3 mmHg and -29 8 beats/min, n=7, respectively) and SHAM animals (-17 3 mmHg and -39 15 beats/min, n=6, respectively). The microinjection of L- ARGININE in the CVLM produced an increase in MAP and variable changes in the HR in 2K1C (11 3 mmHg and -12 6 beats/min, n = 6, respectively) and in the SHAM rats (11 1 mmHg and 8 8 beats/min, n=11, respectively). In 2K1C rats, we observed that the duration of the bradycardia produced by XI microinjection of L-NAME in the CVLM was lower (11 1 min, n=11) than in SHAM animals (23 3 min, n=6). In addition, the duration of the hypertensive effect of microinjection of L- ARGININE in 2K1C rats (26 7 min, n=4) and the variable changes produced by microinjection of L- ARGININE on the HR (32 5 min, n=6) were higher when compared to SHAM rats (10 2 min and 14 4 min, n=7-10, respectively). Cardiovascular effects produced by microinjection of L- ARGININE in the CVLM were abolished by prior microinjection of L-NAME in the CVLM of SHAM and 2K1C rats. The reflex bradycardia sensitivity in 2K1C animals was lower (0.11 0.02 ms / mmHg, n=17) compared to SHAM rats (0.42 0.08 ms / mmHg, n=14). The microinjection of L-NAME in the CVLM produced an increase in the reflex bradycardia sensitivity of 2K1C animals (0.18 0.04 ms / mmHg compared to 0.07 0.01 ms / mmHg, n=10; before LNAME). In addition, the microinjection of L- ARGININE in the CVLM produced a reduction of reflex bradycardia only in SHAM rats (0.29 0.03 ms / mmHg compared to 0.52 0.08 ms / mmHg, n = 6; before L-arginine). The results of this study reinforce the idea that NO participates in the development of hypertension, possibly by increasing its levels in the CVLM. Moreover, these high levels of NO appear to have an inhibitory role on the CVLM neurons, contributing to the low sensitivity of the baroreflex that occurs in the renovascular hypertension.

ASSUNTO(S)

- - fisiologia

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