Xie Fang, Sun Lihua, Su Xiaolin, Wang Ying, Liu Jing, Zhang Rong, Wang Ning, Zhao Jing, Ban Tao, Niu Huifang, Ai Jing
Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratory of Biomedicine-Pharmaceutics of China), Harbin, China.
Cell Physiol Biochem. 2012;29(3-4):463-74. doi: 10.1159/000338500. Epub 2012 Apr 3.
Chronic stress, as a risk factor for cardiovascular diseases, has been reported to result in elevated plasma neuropeptide Y (NPY) and be highly associated with abnormal cardiac autonomic function. This study aimed to explore the effect of NPY on the chronic stress-induced abnormal baroreceptor reflex sensitivity (BRS). Seven types of recognized stressors were used to develop chronic stress rat model. Subcutaneously implanting ALZET mini-osmotic pumps containing NPY were used to evaluate the action of NPY on the stressed male rats. We found that chronic stress showed no influence on baseline systolic blood pressure (SBP) and heart rate (HR), whereas NPY (85 μg for 30 days) could elevate baseline SBP and induce bradycardia in rats intervened by various stimuli. NPY pretreatment could preserve chronic stress-induced decreases in left ventricular systolic pressure (LVSP) and the maximum rate of change in left ventricular pressure in the isovolumic contraction period (+dp/dt(max)) but has shown no effect on left ventricular end diastolic pressure (LVEDP) and the maximum rate of change in left ventricular pressure in the isovolumic relaxation period (-dp/dt(max)). Notably, chronic stress led to baroreflex oversensitivity indicated by the elevated ratio of Δheart rate (HR)/ Δmean arterial blood pressure (MABP) in rats followed by vasoconstrictor (phenylephrine, PE) or vasodilator (sodium nitroprusside, SNP) administration, which was almost completely reversed by NPY pretreatment. The expressions of substance P (SP) and gamma aminobutyric acid A receptor (GABA(A)R) in nucleus tractus solitarius were increased in chronic stress rats, which were counteracted by NPY pretreatment. We conclude that chronic stress-induced baroreflex hypersensitivity could be blocked by NPY pretreatment. Furthermore, the altered expressions of neurotransmitters and receptors in the brainstem might contribute to this process.
慢性应激作为心血管疾病的一个风险因素，据报道会导致血浆神经肽Y（NPY）升高，并与心脏自主神经功能异常高度相关。本研究旨在探讨NPY对慢性应激诱导的压力感受器反射敏感性（BRS）异常的影响。使用七种公认的应激源建立慢性应激大鼠模型。通过皮下植入含有NPY的ALZET微型渗透泵来评估NPY对受应激雄性大鼠的作用。我们发现，慢性应激对基线收缩压（SBP）和心率（HR）没有影响，而NPY（85μg，持续30天）可升高基线SBP并在受到各种刺激干预的大鼠中诱发心动过缓。NPY预处理可维持慢性应激诱导的左心室收缩压（LVSP）降低以及等容收缩期左心室压力最大变化率（+dp/dt(max)）降低，但对左心室舒张末期压力（LVEDP）和等容舒张期左心室压力最大变化率（-dp/dt(max)）没有影响。值得注意的是，慢性应激导致大鼠在给予血管收缩剂（去氧肾上腺素，PE）或血管扩张剂（硝普钠，SNP）后，心率变化（HR）/平均动脉血压变化（MABP）比值升高，表明压力反射超敏，而NPY预处理几乎完全逆转了这种情况。慢性应激大鼠孤束核中P物质（SP）和γ-氨基丁酸A受体（GABA(A)R）的表达增加，而NPY预处理可抵消这种增加。我们得出结论，NPY预处理可阻断慢性应激诱导的压力反射超敏。此外，脑干中神经递质和受体表达的改变可能促成了这一过程。
