Vasodilation effect of volatile oil from Allium macrostemon Bunge are mediated by PKA/NO pathway and its constituent dimethyl disulfide in isolated rat pulmonary arterials

Abstract

The present study aimed to investigate the vasodilation effects of Allium macrostemon Bunge (AMB) on isolated rat pulmonary arterials (PAs) and to assess the underling mechanisms. The volatile oil was extracted by steam distillation from the bulbs of AMB. Then the volatile oil from AMB was studied on isolated rat PA, removal of endothelium, or pretreatment with nitro oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or with protein kinase A (PKA) inhibitor PKI but not cyclooxygenase inhibitor indomethacin significantly blocked the AMB induced relaxation on PE-contracted PA rings. AMB increased the phosphorylation level of NOS in a dose and time-dependent manner, which was through PKA activation. AMB dose-dependently increased the [Ca²⁺]_i through Ca²⁺ influx in cultured pulmonary artery endothelial cells. A total of 18 components from the volatile oil of AMB were identified. The principle constituents of AMB, Dimethyl Disulfide (DMDS) but not Dimethyltrisulfide displayed dilation effects in PAs. Our results suggest that AMB induces relaxation in rat PAs via an endothelium-dependent mechanism involving Ca²⁺ entry, PKA dependent NOS phosphorylation and NO signaling. The vasodilator activities of AMB may through its constituent DMDS. The present study indicates therapeutic potentials of AMB on pulmonary hypertension.

Keywords: Allium macrostemon Bunge; Calcium; Dimethyl disulfide; Nitro oxide; Pulmonary arterials; Vasodilation.