Beneficial effects of γ-aminobutyric acid on right ventricular pressure and pulmonary vascular remodeling in experimental pulmonary hypertension

Abstract

AimsIt has been reported that activation of the sympathetic nervous system and increase in plasma norepinephrine (NE) levels are observed in patients with pulmonary hypertension (PH). γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system and suppresses peripheral sympathetic neurotransmission. This study investigated whether chronic treatment with GABA prevents the development of monocrotaline (MCT)-induced PH. To elucidate the relationship between the development of PH and sympathetic nerve activity, hemodynamic parameters, cardiac functions, and plasma NE concentrations as well as cardiac endothelin-1 (ET-1) contents of MCT-induced PH rats were evaluated with or without GABA treatment. Main methodsRats were injected with MCT (60mg/kg) or saline subcutaneously and these rats were randomly divided into GABA (500mg/kg/day for 4weeks)- or vehicle-treated groups, respectively. Key findingMCT-treated rats had higher right ventricular systolic pressures, right ventricle-to-left ventricle plus septum weight ratios, pulmonary arterial medial thickening, and plasma NE levels than those of saline-injected rats. MCT-induced alternations were significantly attenuated by treatment with GABA. In MCT-induced PH rats with or without GABA treatment, plasma NE levels were positively correlated with right ventricular systolic pressure. Right ventricular endothelin-1 (ET-1) contents were increased by MCT injection, but these increments were not affected by treatment with GABA. SignificanceThese results suggest that plasma NE levels play an important role in the development of MCT-induced PH in rats and that GABA exerts a preventive effect against MCT-induced PH by suppressing the sympathetic nervous system but not the cardiac ET-1 system.