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Effect of β-adrenergic Activity on the express of Neurokinin-1 Receptor in Heart in Acute Myocardial Infarction in Rats

Author: HanShiZuo
Tutor: GuoZheng
School: Shanxi Medical
Course: Anesthesiology
Keywords: neurokinin-1 receptor(NK1-R) SP DSP esmolol myocardial ischemia
CLC: R541
Type: Master's thesis
Year: 2011
Downloads: 21
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Abstract


Background Substance P is a member of the family of structurally related peptides named tachykinins and is localised to the sensory nerves of the heart in various species including man. The presence and the release of SP by different stimuli in the heart are consistent with the opinion that SP may be involved in modulating cardiac functions. There are three subtypes of tachykinin receptors, NK1, NK2, and NK3 that belong to the G protein-coupled receptor family (GPCRs).Although SP can activate all three tachykinin receptors, its potency is greatest at NK1 receptor (NK1-R) .Cardiac effect of SP may be mediated by the NK1 receptor, which has been found existent in the heart. Evidence indicated that SP and neurokinin-1 (NK-1) receptor were involved in the transmission of neural afferents of C fibers and in the mediation of the noxious neural signals of acute myocardial ischemia in spinal cord and myocardium.Studies indicate that activation of sympathetic nervous system and cardiac sensory afferent nerves could be timely overlapped in acute myocardial ischemia, presenting massive increase in the catecholamines and some neuropeptides, including substance P (SP), which may be associated with the pathology of acute myocardial ischemia and infarction. Our previous experiments also showed that substance P, and NE were simultaneously up-regulated at early time of acute myocardial ischemia. However a potential effect of adrenergic in modulation of NK1-R in acute myocardial ischemia is elusive.We designed this study to investigate the potential modulation of NK1 receptor by endogenousβ1-adrenergic activity during the early stage of acute myocardial ischemia in rats by characterizing the changes of NK1-R (the mRNA and proteins) in the animals with and without pretreatment of a specific antagonist ofβ1-adrenoceptor receptor, in acute myocardial ischemia induced by the permanent coronary occlusion (CAO).Objective Evidence suggests that substance P regulates of pathology of acute myocardial ischemia and infarction via neurokinin-1 receptor (NK1 receptor, NK1-R). But the expression of NK1 receptor alteration during the acute phases of myocardial ischemia is still elusive. The aim of this study was to show the change of expression of NK1 at the mRNA level and protein level and relation with adrenergic mechanism at the early stage of myocardial ischemia.Methods :The study was carried out in two parts:1,Expressions of NK1-R:Thirty-six animals were used for the examination of the changes in the NK1-R mRNA using quantitative reverse transcription-PCR (qRT-PCR) at 5 min (n = 6), 15 min (n = 6) and 30 min (n = 6) of the CAO and sham surgery (n = 18, 6 rats in each subgroup). And another thirty-six animals were used to detect the difference in the protein density of NK1-R using western blot at 15 min (n=6), 30min (n=6) and 60min (n=6) of the CAO and sham surgery (n=18, 6 rats in each subgroup).2,Effects of esmolol on the expressions of NK1-R:Eighteen animals were divided into three groups to examine the changes of the NK1-R mRNA, under the condition: (1) given 1ml/Kg of 0.9% saline (i.v.) at 15 min before onset of a period of 15 min of coronary artery occlusion (CAO, n = 6), (2) pretreatment with a specific antagonist ofβ1-adrenoceptor,Esmolol hydrochloride, (QiLu medicines company,JiNan,China), at a concentration of 10-7 Mol/L (1ml/kg, i.v.) at 15min before CAO (ESM, n = 6). (3) pretreatment with a specific antagonist of NK1-R,[D-Arg1, D-Phe5, D-Trp7,9, Leu11]-Substance P (D-SP) (Sigma-Aldrich Corp. St. Louis, MO, USA), at a concentration of 10-7 Mol/L (1ml/kg, i.v.) at 15min before CAO (ESM, n = 6). Another 18 animals were assigned to two groups under the same regime, CAO (n = 6), DSP (n=6) and ESM (n = 6), for the analysis of the changes in the protein density of NK1-R.Results :. No statistical difference was detected in the expressions of the NK1-R proteins and mRNA between the sham group and the CAO group at the early stage of myocardial ischemia. Pretreatment CAO group rats with a specific antagonist ofβ1-adrenoceptor, esmolol, the expression of NK1-R (protein and mRNA) lever was increased significantly. Pretreatment CAO group rats with DSP, the expression of NK1-R (protein and mRNA) lever was also increased significantly.Conclusion: Expression of NK1-R had no significantly alteration in myocardium during the acute phases of myocardial ischemia. Sympathetic and cardiac sensory nervous system may

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease
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