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Water extract of Imperatae Rhizom induces vascular relaxation via NO‐cGMP‐PKG signaling
Author(s) -
Kim Hye Yoom,
Ahn You Mee,
Jin Xian Jun,
Hong Mi Hyeon,
Kim Hyun Ju,
Yang Sun Nye,
Lee Yun Jung,
Lee Ho Sub,
Kang Dae Gill
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.835.10
Subject(s) - wortmannin , enos , phenylephrine , nitric oxide , endothelium , pharmacology , umbilical vein , chemistry , endocrinology , medicine , protein kinase b , nitric oxide synthase , signal transduction , biochemistry , blood pressure , in vitro
The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)‐mediated property of the aqueous extract of Imperatae Rhizoma (AIR), pronounced anti‐inflammatory herb, in vascular endothelium. The roles of the NO signaling in the AIR‐induced effects were tested in human umbilical vein endothelial cells (HUVECs) and aortic ring. HUVEC treated with AIR produced higher amount of NO compared to control. AIR increased in the expression and phosphorylation levels of eNOS and Akt in HUVECs, which were attenuated by L‐NAME, a NOS inhibitor, and wortmannin, a PI3K inhibitor. mRNA or protein levels of guanosine triphosphate cyclohydrolase I (GTPCH) was upregulated in HUVECs treated with AIR, suggesting a role of eNOS coupling. In addition, AIR‐induced dose‐dependent relaxation of phenylephrine‐precontracted aorta was abolished by removal of functional endothelium. Pretreatment with L‐NAME, and ODQ inhibited the AIR‐induced vasorelaxation. Wortmannin and LY‐294002 an upstream signaling molecule of eNOS, attenuated the AIR‐induced vasorelaxation. Incubation of endothelium‐intact aortic rings with AIR increased the production of cGMP, however, which were attenuated by L‐NAME and ODQ. Two‐kidney‐one‐clip (2K1C) hypertensive rats were established to investigate the hypotensive effect of AIR in renovascular hypertension. 2K1C rats were treated with AIR at dose of 100 mg/kg/day orally for 3 weeks. AIR significantly lowered blood pressure. Interestingly, AIR ameliorated both endothelium‐dependent and independent vascular relaxation in the phenylephrine‐precontracted thoracic aorta. 2K1C‐induced hypertension model increased plasma renin activity, however, AIR attenuated those activities. Taken together, the present study suggests that AIR ameliorates vascular dysfunction via the regulation of renin‐angiotensin system and endothelium‐dependent activation of through the PI3K/Akt‐mediated NO‐cGMP‐PKG signaling. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2008‐0062484).