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自发性高血压大鼠颈动脉体和自主神经节中的纤溶酶原激活物抑制剂-1和转化生长因子-β1

Plasminogen activator inhibitor-1 and transforming growth factor-beta 1 in carotid glomus and autonomic ganglia from spontaneously hypertensive rats.

作者信息

Milei José, Cao Gabriel, Grana Daniel R, Toblli Jorge E

机构信息

Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini, Universidad de Buenos Aires, Argentina.

出版信息

J Hypertens. 2004 Jul;22(7):1351-9. doi: 10.1097/01.hjh.0000125434.28861.9b.

DOI:10.1097/01.hjh.0000125434.28861.9b
PMID:15201552
Abstract

BACKGROUND

Baroreflex and chemoreflex mechanisms play an important role in the dynamic adjustments of circulation and ventilation during daily life. Recently, we have observed atrophy and marked fibrosis in carotid glomus (CG) from old patients with carotid atherosclerosis who died following stroke. However, a possible limitation to interpretation of the results in that study was the superposition of arterial hypertension, atherosclerosis and aging in the patients. Taking this into account, spontaneously hypertensive rats (SHR) were used in order to study the CG in an experimental model with only hemodynamic stress.

OBJECTIVE

To evaluate whether transforming growth factor-beta 1 (TGF-beta 1) and plasminogen activator inhibitor-1 (PAI-1) were involved in the extracellular matrix expansion in CG and autonomic ganglia (AG) in young, male, adult SHR.

METHODS

Male SHR (n = 10) and Wistar-Kyoto (WKY) rats (n = 10) were used. Systolic blood pressure (SBP) was measured monthly up to 8 months of age, when the animals were killed; then, CG and AG were excised and processed for light microscopy and immunohistochemistry (TGF-beta 1, PAI-1 and protein S100).

RESULTS

SBP was highly correlated (P < 0.01) with CG fibrosis (r = 0.90), AG fibrosis (r = 0.96) and neuron number (r = -0.97). PAI-1 and TGF-beta 1 in CG and AG were significantly increased (P < 0.01) in SHR.

CONCLUSION

Severe damage was observed in CG and AG in SHR, which was, in addition, correlated with SBP. These results suggest that permanent high blood pressure produces remarkable lesions in these structures, even when the animals are not old. In view of the fact that CG and AG are of utmost importance in the genesis of cardiocirculatory reflexes, they might be considered as 'target organs' in arterial hypertension.

摘要

背景

压力反射和化学反射机制在日常生活中循环和通气的动态调节中起重要作用。最近,我们在死于中风的老年颈动脉粥样硬化患者的颈动脉体(CG)中观察到萎缩和明显纤维化。然而,该研究结果解释的一个可能局限性是患者中存在动脉高血压、动脉粥样硬化和衰老的叠加。考虑到这一点,为了在仅存在血流动力学应激的实验模型中研究CG,使用了自发性高血压大鼠(SHR)。

目的

评估转化生长因子-β1(TGF-β1)和纤溶酶原激活物抑制剂-1(PAI-1)是否参与年轻成年雄性SHR的CG和自主神经节(AG)细胞外基质扩张。

方法

使用雄性SHR(n = 10)和Wistar-Kyoto(WKY)大鼠(n = 10)。每月测量收缩压(SBP)直至动物8个月龄时处死;然后,切除CG和AG并进行光学显微镜检查和免疫组织化学检查(TGF-β1、PAI-1和蛋白质S100)。

结果

SBP与CG纤维化(r = 0.90)、AG纤维化(r = 0.96)和神经元数量(r = -0.97)高度相关(P < 0.01)。SHR的CG和AG中的PAI-1和TGF-β1显著增加(P < 0.01)。

结论

在SHR的CG和AG中观察到严重损伤,此外,这与SBP相关。这些结果表明,即使动物未衰老,持续性高血压也会在这些结构中产生明显病变。鉴于CG和AG在心脏循环反射的发生中至关重要,它们可能被视为动脉高血压中的“靶器官”。

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