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Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus.
Hypertension. 2016 07; 68(1):175-84.H

Abstract

Renal denervation (RDN) has been postulated to reduce sympathetic drive during heart failure (HF), but the central mechanisms are not completely understood. The purpose of the present study was to assess the contribution of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN) in modulating sympathetic outflow in rats with HF that underwent RDN. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, bilateral RDN was performed. Rats with HF had an increase in FosB-positive cells in the PVN with a concomitant increase in urinary excretion of norepinephrine, and both of these parameters were ameliorated after RDN. nNOS-positive cells immunostaining, diaphorase staining, and nNOS protein expression were significantly decreased in the PVN of HF rats, findings that were ameliorated by RDN. Microinjection of nNOS inhibitor N(G)-monomethyl l-arginine into the PVN resulted in a blunted increase in lumbar sympathetic nerve activity (11±2% versus 24±2%) in HF than in sham group. This response was normalized after RDN. Stimulation of afferent renal nerves produced a greater activation of PVN neurons in rats with HF. Afferent renal nerve stimulation elicited a greater increase in lumbar sympathetic nerve activity in rats with HF than in sham rats (45±5% versus 22±2%). These results suggest that intact renal nerves contribute to the reduction of nNOS in the PVN, resulting in the activation of the neurons in the PVN of rats with HF. RDN restores nNOS and thus attenuates the sympathoexcitation commonly observed in HF.

Authors+Show Affiliations

From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha. kpatel@unmc.edu.From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha.From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha.From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha.From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27185748

Citation

Patel, Kaushik P., et al. "Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: a Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus." Hypertension (Dallas, Tex. : 1979), vol. 68, no. 1, 2016, pp. 175-84.
Patel KP, Xu B, Liu X, et al. Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. Hypertension. 2016;68(1):175-84.
Patel, K. P., Xu, B., Liu, X., Sharma, N. M., & Zheng, H. (2016). Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. Hypertension (Dallas, Tex. : 1979), 68(1), 175-84. https://doi.org/10.1161/HYPERTENSIONAHA.115.06794
Patel KP, et al. Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: a Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. Hypertension. 2016;68(1):175-84. PubMed PMID: 27185748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal Denervation Improves Exaggerated Sympathoexcitation in Rats With Heart Failure: A Role for Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus. AU - Patel,Kaushik P, AU - Xu,Bo, AU - Liu,Xuefei, AU - Sharma,Neeru M, AU - Zheng,Hong, Y1 - 2016/05/16/ PY - 2015/11/09/received PY - 2016/04/15/accepted PY - 2016/5/18/entrez PY - 2016/5/18/pubmed PY - 2017/7/20/medline KW - central nervous system KW - heart failure KW - neurons KW - nitric oxide synthase KW - sympathetic nervous system SP - 175 EP - 84 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 68 IS - 1 N2 - Renal denervation (RDN) has been postulated to reduce sympathetic drive during heart failure (HF), but the central mechanisms are not completely understood. The purpose of the present study was to assess the contribution of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN) in modulating sympathetic outflow in rats with HF that underwent RDN. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, bilateral RDN was performed. Rats with HF had an increase in FosB-positive cells in the PVN with a concomitant increase in urinary excretion of norepinephrine, and both of these parameters were ameliorated after RDN. nNOS-positive cells immunostaining, diaphorase staining, and nNOS protein expression were significantly decreased in the PVN of HF rats, findings that were ameliorated by RDN. Microinjection of nNOS inhibitor N(G)-monomethyl l-arginine into the PVN resulted in a blunted increase in lumbar sympathetic nerve activity (11±2% versus 24±2%) in HF than in sham group. This response was normalized after RDN. Stimulation of afferent renal nerves produced a greater activation of PVN neurons in rats with HF. Afferent renal nerve stimulation elicited a greater increase in lumbar sympathetic nerve activity in rats with HF than in sham rats (45±5% versus 22±2%). These results suggest that intact renal nerves contribute to the reduction of nNOS in the PVN, resulting in the activation of the neurons in the PVN of rats with HF. RDN restores nNOS and thus attenuates the sympathoexcitation commonly observed in HF. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/27185748/Renal_Denervation_Improves_Exaggerated_Sympathoexcitation_in_Rats_With_Heart_Failure:_A_Role_for_Neuronal_Nitric_Oxide_Synthase_in_the_Paraventricular_Nucleus_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.115.06794?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -