Premium
Oroxylin A‐induced Endothelium‐dependent Constriction of Tail Arteries of Endotoxemic Hypotensive Rats
Author(s) -
Tseng TzuLing,
Chen MeiFang,
Liu ChinHung,
Lee Tony
Publication year - 2015
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.29.1_supplement.626.7
Subject(s) - constriction , rhoa , vasoconstriction , endothelium , endothelin receptor , lipopolysaccharide , vascular smooth muscle , medicine , pharmacology , shock (circulatory) , endocrinology , chemistry , receptor , smooth muscle , signal transduction , biochemistry
Refractory hypotension and vascular hyporeactivity in severe sepsis remain major clinical concerns. Here we report the induction of endothelium‐dependent constriction of tail arteries (TA) in endotoxemic hypotensive rats. In lipopolysaccharide (LPS)‐induced endotoxemic rats, oroxylin A (OroA, 15 mg/kg, iv) administered 6 hrs after LPS‐challenge promptly reversed diminished mean arterial pressure(MAP) and heart rate. OroA (1‐10 µM), which did not constrict isolated normal TA, repeatedly induced exclusive endothelium‐dependent, sustained constriction of isolated endotoxemic TA with intact‐endothelium (EC+). OroA‐induced constriction of was not blocked by endothelin‐1 (ET‐1) receptor antagonists (BQ123 or BQ788, 10 µM), but was blocked by inhibitors for RhoA/ROCK pathway. These results suggest that OroA‐induced endothelium‐dependent constriction of endotoxemic TA is mediated by non‐ET‐1‐substance(s) which activated muscle RhoA/ROCK pathway. OroA‐post‐treatment also suppressed, via inhibition of NF‐κB, inducible‐NOS expression and circulating NO. It is concluded that LPS upregulates endothelial non‐ET‐1‐vasoconstrictor(s) in endotoxemic TA. Its release by OroA activates muscle RhoA/ROCK pathway leading to prompt and sustained vasoconstriction that partly is caused by decreased circulating NO induced by OroA. The endothelium‐dependent constriction of TA and suppression of systemic inflammation as evidenced by OroA may offer a newstrategy for acute management of endotoxemic hypotensive shock (supported by MOST, TCU, and Tzu Chi Foundation).