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Pharmacological intervention to the endotoxemia‐induced arterial hyporeactivity to vasoconstrictors
Author(s) -
Zhang Shuang,
Cui Ningren,
Li Shanshan,
Wu Yang,
Jiang Chun
Publication year - 2013
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.27.1_supplement.689.10
Subject(s) - vasodilation , phenylephrine , vasoconstriction , medicine , contractility , nitric oxide , vascular smooth muscle , mesenteric arteries , septic shock , hypoxia (environmental) , shock (circulatory) , sepsis , pharmacology , chemistry , smooth muscle , blood pressure , artery , organic chemistry , oxygen
People with septic shock develop uncontrolled hypotension leading to hypoperfusion, tissue hypoxia, multiple organ failure and death. It is unclear what causes the excessive vasodilation and vascular hyporeactivity to circulating vasoconstrictors in sepsis. The vascular responses may result from a loss of contractility of vascular smooth muscle (VSM) cells, enhanced VSM response to vasodilators, or depressed VSM response to vasoconstrictors. To test these possibilities, we performed these studies on isolated and perfused mesenteric arterial rings. A 20‐h exposure of the rings to bacterial endotoxins (LPS, 1μg/ml) led to marked hyporeactivity of the rings to phenylephrine (PE). However, the responses of the LPS‐treated rings to high concentrations of KCl remained comparable to the control rings, suggesting that the VSM contractility is retained. The hyporeactivity was barely affected by atropine, indomethacin and nitric oxide synthase inhibitor L‐NAME, suggesting that the endothelium‐dependent vasorelaxation does not appear to play a major role. Several vasoconstrictors were tested. With LPS treatment rings were hyporeactive to certain vasoconstrictors but constricted well in response to others. Although rings were hyporeactive to some of the vasoconstrictors, their vasoconstriction effects were significantly potentiated by a joint application with PE. These results suggest that a loss of sensitivities to certain vasoconstrictors appears crucial for the endotoxemic vasodilation and vascular hyporeactivity. (supported by NIH R01‐NS073875 and the MBD program of GSU)