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Cervical Ganglion Block Attenuates the Progression of Pulmonary Hypertension via Nitric Oxide and Arginase Pathways

Authors
 Sungwon Na  ;  Ok Soo Kim  ;  Sungwoo Ryoo  ;  Tae Dong Kweon  ;  Yong Seon Choi  ;  Hyo Sup Shim  ;  Young Jun Oh 
Citation
 Hypertension, Vol.63(2) : 309-315, 2014 
Journal Title
 Hypertension 
ISSN
 0194-911X 
Issue Date
2014
MeSH
Amides/pharmacology* ; Anesthetics, Local/pharmacology ; Animals ; Arginase/antagonists & inhibitors ; Arginase/metabolism ; Autonomic Nerve Block/methods* ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Cardiomegaly/drug therapy ; Cardiomegaly/metabolism ; Cardiomegaly/physiopathology ; Ganglia, Sympathetic/drug effects* ; Ganglia, Sympathetic/metabolism ; Ganglia, Sympathetic/physiopathology ; Hypertension, Pulmonary/drug therapy* ; Hypertension, Pulmonary/metabolism ; Male ; Monocrotaline/pharmacology* ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Rats ; Rats, Sprague-Dawley ; Superior Cervical Ganglion/drug effects* ; Superior Cervical Ganglion/metabolism ; Superior Cervical Ganglion/physiopathology
Keywords
autonomic pathways ; hypertension, pulmonary ; nitric oxide ; sympathetic nervous system
Abstract
It has been recognized that the sympathetic nervous system is activated in pulmonary arterial hypertension (PAH), and abnormal sympathetic hyperactivity leads to worsening of PAH via endothelial dysfunction. The purpose of this study was to examine whether sympathetic ganglion block (SGB) can treat PAH by increasing the availability of nitric oxide (NO). PAH was induced in rats by 50 mg/kg of subcutaneous monocrotaline. After 2 weeks, daily injections of ropivacaine into the left superior cervical ganglion were repeated for 14 days (monocrotaline-SGB group). Monocrotaline group received sham SGB with saline, whereas control group received saline instead of monocrotaline. PAH was evident in monocrotaline group, with right ventricular systolic pressures (47±4 mm Hg) that were higher than those of controls (17±2 mm Hg), whereas SGB significantly attenuated monocrotaline-induced PAH (35±4 mm Hg). The right/left ventricular mass ratios exhibited similar changes to those seen with right ventricular pressures. Heart rate variability showed significantly higher sympathetic activity in the monocrotaline group. Microscopy revealed a higher proportion of muscular arteries with thicker medial walls in the monocrotaline group, which was attenuated by SGB. Monocrotaline induced arginase hyperactivity, which was in turn decreased by SGB-induced endothelial NO synthase activation. SGB restored monocrotaline-induced hypoactivity of superoxide dismutase. In conclusion, SGB could suppress PAH and the remodeling of pulmonary arteries via inactivation of arginase and reciprocal elevation of NO bioavailability, thus attenuating disproportionate hyperactivation of the sympathetic nervous system.
Full Text
http://hyper.ahajournals.org/content/63/2/309.long
DOI
10.1161/HYPERTENSIONAHA.113.01979
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kweon, Tae Dong(권태동) ORCID logo https://orcid.org/0000-0002-5451-1856
Kim, Ok Soo(김옥수)
Na, Sungwon(나성원) ORCID logo https://orcid.org/0000-0002-1170-8042
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Oh, Young Jun(오영준) ORCID logo https://orcid.org/0000-0002-6258-5695
Choi, Yong Seon(최용선) ORCID logo https://orcid.org/0000-0002-5348-864X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99281
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