title: Cervical ganglion block attenuates the progression of pulmonary hypertension via nitric oxide and arginase pathways.
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.
authors: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, Seoul 120-752, Republic of Korea. yjoh@yuhs.ac.
authors: Sungwon
authors: S
authors: Na
authors: Ok Soo
authors: OS
authors: Kim
authors: Sungwoo
authors: S
authors: Ryoo
authors: Tae Dong
authors: TD
authors: Kweon
authors: Yong Seon
authors: YS
authors: Choi
authors: Hyo Sup
authors: HS
authors: Shim
authors: Young Jun
authors: YJ
authors: Oh
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001340:Autonomic Nerve Block / Q000379:methods*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D009569:Nitric Oxide; D016686:Monocrotaline; D000077212:Ropivacaine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001119:Arginase
keywords: autonomic pathways; hypertension, pulmonary; nitric oxide; sympathetic nervous system