ERK1/2 Mediated The Vasodilatation of Apelin-13 on Vascular Rings of Spontanously Hypertensive Rat in vitro

作者:Liu Chang Hui; Li Xin; Chen Feng; Pan Wei Nan; Feng Fen; Qin Xu Ping; Li Lan Fang; Su Tao; Chen Lin Xi*
来源:Progress in Biochemistry and Biophysics, 2009, 36(12): 1578-1588.
DOI:10.3724/SP.J.1206.2009.00360

摘要

In order to study the effect of G protein-coupled receptor APJ endogenous ligand apelin-13 to the vasoconstriction and relaxation of spontaneously hypertensive rat's vascular rings in vitro and its NO and ERK1/2 pathway, perfusion method in vitro vascular ring and Power-Lab system was used to detect tension on rat's vascular rings. Experimental groups below: Phenylephrine group, Acetylcholine group, apelin-13 group, apelin-13+ PE group, apelin-13+Ach group, PD98059+PE group, PD98059+Ach group, LNNA+PE group, LNNA+Ach group, apelin-13 (preincubation) +PD98059 +PE group, apelin (preincubation)-13 +PD98059 +Ach group, apelin-13 (preincubation)+LNNA+PE group and apelin-13 (preincubation)+LNNA+Ach group, compared with WKY rats. Rats' vascular smooth muscle cells were cultured and the expression of ERK1/2 protein was detected by Western blot. Apelin-13 for the blood vessel with endothelium has demonstrated concentration-dependent vasodilation and SHR < WXY in percentage vasodilation, but for the blood vessel without endothelium, apelin-13 shows the role of vascular contraction and SHR > WKY in contraction tension. Apelin-13 pre-incubation can reduce the SHR and WKY rats' the reactivity of vascular contraction tension on phenylephrine and increases the relaxation response to acetylcholine. After NOS inhibitors LNNA blocking the formation of NO, the relaxation response of the vascular rings to apelin-13 is significantly inhibited and apelin more pronounced reduces the diastolic response in the SHR group than in the WKY group. This suggests that the vasodilator effect of apelin-13 partly depends on NO-dependent pathway at least and SHR hypertensive rats with NO pathway obstacles reduces the vasodilation of blood vessels to apelin-13. After pre-incubation of ERK1/2 inhibitor PD98059, the response of vascular rings to apelin-13 shows concentration-dependent contraction, which is the same as the blood vessel without endothelium to apelin-13, SHR > WKY in contraction tension. PD98059 reversals the apelin-13's vasodilation effect. Western blot analysis showed that apelin-13 promoted the concentration-dependent and time-dependentexpression of pERK1/2. The potent ERK inhibitor PD98059 decreased the expression of pERK1/2. The diastolic reactivity of apelin in ex-vivo vascular rings of SHR is reduced and the effect is mediated by NO pathway and the ERK1/2 pathway.