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The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats.
Nitric Oxide. 2018 09 01; 79:14-24.NO

Abstract

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (†P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, †P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (†P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (†P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats.

Authors+Show Affiliations

Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil; Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil; Departament of Pathological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.Departament of Pathological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address: martinspinge@uel.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29983399

Citation

Raquel, Hiviny de Ataides, et al. "The Essential Role of Hypothalamic Paraventricular Nucleus nNOS in the Modulation of Autonomic Control in Exercised Rats." Nitric Oxide : Biology and Chemistry, vol. 79, 2018, pp. 14-24.
Raquel HA, Ferreira NZ, Lucchetti BFC, et al. The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats. Nitric Oxide. 2018;79:14-24.
Raquel, H. A., Ferreira, N. Z., Lucchetti, B. F. C., Falquetto, B., Pinge-Filho, P., Michelini, L. C., & Martins-Pinge, M. C. (2018). The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats. Nitric Oxide : Biology and Chemistry, 79, 14-24. https://doi.org/10.1016/j.niox.2018.07.002
Raquel HA, et al. The Essential Role of Hypothalamic Paraventricular Nucleus nNOS in the Modulation of Autonomic Control in Exercised Rats. Nitric Oxide. 2018 09 1;79:14-24. PubMed PMID: 29983399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats. AU - Raquel,Hiviny de Ataides, AU - Ferreira,Nathalia Zerbinatti, AU - Lucchetti,Bruno Fernando Cruz, AU - Falquetto,Bárbara, AU - Pinge-Filho,Phileno, AU - Michelini,Lisete Compagno, AU - Martins-Pinge,Marli Cardoso, Y1 - 2018/07/03/ PY - 2018/02/16/received PY - 2018/05/24/revised PY - 2018/07/02/accepted PY - 2018/7/10/pubmed PY - 2019/4/2/medline PY - 2018/7/10/entrez KW - Baroreflex sensitivity KW - Neuronal nitric oxide synthase KW - Nitric oxide KW - Paraventricular nucleus of the hypothalamus KW - Swimming training KW - l-arginine supplementation SP - 14 EP - 24 JF - Nitric oxide : biology and chemistry JO - Nitric Oxide VL - 79 N2 - Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (†P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, †P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (†P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (†P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats. SN - 1089-8611 UR - https://www.unboundmedicine.com/medline/citation/29983399/The_essential_role_of_hypothalamic_paraventricular_nucleus_nNOS_in_the_modulation_of_autonomic_control_in_exercised_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089-8603(18)30046-6 DB - PRIME DP - Unbound Medicine ER -