Contractile effect and mechanism of 15-HETE on hypoxic rat ICA rings / 中国药理学通报

ABSTRACT

Aim To evaluate the effect of 15-hydroxy eicosatetraenoic acid(15-HETE) on the tension of isolated internal carotid artery(ICA) rings in normoxic or hypoxic rats in order to find out the pathophysiological effect of 15-HETE in ischemic/hypoxic brain tissues.Methods Sixteen healthy Wistar rats were randomly divided into two groups(n=8) group A with normal oxygen supply(FiO_2 21%) and group B with hypoxia(FiO_2 10%).9 days later,the rats were killed and the ICA rings were prepared.15-HETE in different concentration were added accordingly,and the after washing up,blockers of different kinds of K~+ channels such as 2 mmol?L~(-1) 4-AP,10~(-2) mol?L~(-1) TEA and 10~(-6) mol?L~(-1) GLYB were added to the KH solution separately,followed by the administration of 10~(-6) mol?L~(-1) 15-HETE.The isometric tension was recorded using a four-channel force-displacement transducer.Results The ICA tension was significantly increased both in groups A and B by 15-HETE in concentration-dependent manner(P0.05,n=8).Furthermore,10~(-2) mol?L~(-1) TEA,10~(-6) mol?L~(-1) GLYB had little effects on the tension of rings.Application of 10~(-6) mol?L~(1) 15-HETE after administration of TEA or GLYB induced nearly the same increase in ICA tone as it happened in the group administered with 10~(-6)mol?L~(-1) 15-HETE alone.Conclusion 15-HETE can induce brain vasoconstriction especially under the hypoxic condition.Voltage-dependent potassium channels play an important role in 15-HETE induced constriction.