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

Abstract

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 monocrotalineinduced 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 have been reported to attenuate the severity of symptoms and slow the progression of cardiovascular diseases including coronary artery disease, heart failure, and arrhythmias. According to the previous reports, there is a possibility that direct sympathetic nerve blocks are effective in patients with myocardial ischemia or systemic hypertension. 17,19 Given the relationship between sympathetic nervous system hyperactivity and endothelial dysfunction in patients with PAH, blockade of sympathetic hyperactivity may improve vascular reactivity by preserving endothelial function. To date, however, there is limited amount of data on the therapeutic effects of sympathetic ganglion block (SGB) on PAH. The purpose of the present study is to assess the therapeutic effects of SGB in a monocrotaline-induced PAH rat model. In parallel, we investigated whether SGB could attenuate the changes in arginase and NO bioavailability, as well as oxidative stress caused by monocrotaline. MethodsDetailed methods about animal preparation, experimental design, SGB, heart rate variability, hemodynamic analysis, right ventricular mass, pulmonary vessel morphometry, and NO (synthase)/arginase/ cGMP/oxidative stress assay are described in the online-only Data Supplement. Results Right Ventricular Systolic Pressure and Right Ventricular/Left Ventricular Mass RatioRight ventricular systolic pr...

Assessment of serum arginase I as a type 2 diabetes mellitus diagnosis biomarker in patients

“…Arginase II is expressed in the mitochondria of extrahepatic cells and is encoded by a different gene (3). The two arginases are constitutively expressed in cells and tissues, and indirectly regulate nitric oxide (NO) generation from nitric oxide synthase (NOS) by competition for a common enzyme substrate (4,5). Therefore, the induction of NOS arginase has been investigated in the inflammatory cells of asthmatic lungs as pathophysiological evidence that the consumption of L-arginine by arginase may lead to the depletion of NO production and endothelial dysfunction; thus, the enlargement of bronchial smooth muscle associated with airway hyperresponsiveness (6–8).…”

Antioxidation Role of Different Lateral Stellate Ganglion Block in Isoproterenol-Induced Acute Myocardial Ischemia in Rats

“…Tissue acidosis occurring during ischemia increases NO production. 50 Otherwise, in inflammatory conditions caused by AMI, 51 it produces a high concentration of NO, forming oxidative stress injury. The findings of the previous study were that direct SGB increased NO bioavailability and decreased the NO expression in cardiac tissue.…”

“…52 In our research, we found that SGB increased eNOS and nNOS expression, which was similar to previous literature reports. 51,52 The reasons for the inconsistency with regulating expression of NO and eNOS and nNOS were as follows: First, the increased NO was reduced by consumption of oxidative reaction. Nitric oxide-producing enzymes, such as the eNOS and nNOS expression of the protein and mRNA, were increased by SGB.…”

Hypertension Editors’ Picks

“…Potentially important signaling pathways highlighted include microRNAs, 1,2 myocardin-related transcription factor A, 3 kinins, 4 estradiol, 5 leukotrienes, 6 tumor necrosis factor-α, 7 nuclear factor-κB, 8 oxidative stress, 9,10 TWIK-2 potassium channels, 11 and transient receptor potential channels. 12 Two articles 13,14 focus on possible adverse impacts of the sympathetic nervous system activation known to accompany PAH. Two studies were designed to improve the pharmacological management of PAH using novel drug delivery strategies.…”