Dihydromyricetin improves vascular hyporesponsiveness in experimental sepsis via attenuating the over-excited MaxiK and K channels.

Context: Dihydromyricetin (DMY) has oxidation resistance, anti-inflammatory and free radical scavenging capabilities. The preventive effects of DMY for vascular hyporeactivity remain unclear.

Objective: This study investigates the preventive effects of DMY in vascular hyporeactivity.

Materials And Methods: The experimental sepsis was induced by transvenous administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. DMY-treated rats received daily administration of DMY, 5 μg/kg dissolved in DMSO through the tail vein for 7 days. The invasive mean arterial pressure (MAP) of the caudal ventral artery was measured. Dose-response curves for norepinephrine (NE, doses from 10 to 10M) were obtained in isolated thoracic aorta in a cumulative manner. The function of MaxiK and K channels were investigated using whole-cell patch clamp recording. The Elisa was adopted to measure the serum concentration of NO, MDA, 3-NT, IL-1β and TNF-α.

Results: The increased MAP in septic rats induced by vasopressor agents was smaller than that in control rats. However, the % of increased MAP induced by vasopressor agents was raised by DMY injection (NE: 20.4 ± 8.495 vs. 15.16 ± 5.195%; AVP: 14.05 ± 2.459 vs. 9.583 ± 2.982%, p < 0.05). The vascular hyporesponsiveness to NE (10M) in vitro. was increased by 51% in LPS + DMY group compared with that in LPS + Con group (2.74 ± 0.81 vs. 1.82 ± 0.92 g, p < 0.05). Charybdotoxin (a potent MaxiK channel blocker) and glibenclamide (a K channel blocker) pretreatment, instead of 4-aminopyridine (4-AP) and BaCl, could diminish the DMY-induced improvement of vasoconstrictor hyporeactivity (ChTX: 73.2 ± 11.8 vs. 71.8 ± 13.5%; Glib: 63.1 ± 12.5 vs. 58.1 ± 13.7%, p > 0.05). DMY blunted the highly sensitized MaxiK and K channels of arterial smooth muscle cells isolated from the thoracic aorta of LPS rats. DMY decreased the serum level of NO, MDA, IL-1β and TNF-α, which had increased in LPS rats.

Discussion And Conclusions: Our results indicate that DMY administration ameliorated the impaired contractility of the rat aorta in experimental sepsis. Such an effect is mediated by normalization of the over-excited MaxiK and K, channels possibly via oxidative stress inhibition.