去甲肾上腺素刺激自发性高血压大鼠动脉中肌醇磷酸的积累。

Noradrenaline-stimulated inositol phosphate accumulation in arteries from spontaneously-hypertensive rats.

作者信息

Guild S B, Jenkinson S, Muir T C

机构信息

Department of Pharmacology, University of Glasgow.

出版信息

Br J Pharmacol. 1992 Aug;106(4):859-64. doi: 10.1111/j.1476-5381.1992.tb14425.x.

DOI:10.1111/j.1476-5381.1992.tb14425.x

PMID:1393285

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907654/

Abstract

The effects of noradrenaline upon polyphosphoinositide (PPI) breakdown was investigated by measuring the accumulation of inositol phosphates (IPs) in tail arteries from normo- (WKY) and spontaneously-hypertensive (SHR) rats. 2. Noradrenaline (10(-7)-10(-3) M) evoked a concentration-dependent increase in total IP accumulation in both WKY and SHR rats but no significant differences between the populations were detected. 3. In contrast, significant differences in the accumulation of the individual IPs, which contributed to the total IP, occurred. A significantly greater noradrenaline-stimulated accumulation of inositol trisphosphate (IP3) was observed in tissues from SHR compared with those from WKY rats at each effective concentration of noradrenaline. This was paralleled by an equivalent reduction in inositol monophosphate (IP1) accumulation, consistent with the lack of a significant difference in noradrenaline-stimulated total IP accumulation between the two populations. 4. In time course studies, an enhanced noradrenaline-induced accumulation of IP3, in SHR compared to WKY rats, occurred from the earliest time point studied after the addition of the catecholamine both in the presence and absence of LiCL (10 mM). In the presence of LiCl (10 mM) no significant difference in noradrenaline-evoked total IP accumulation between SHR and WKY rats was observed; in the absence of LiCl noradrenaline-evoked a greater total IP accumulation in SHR than in WKY rats at all time points investigated. 5. These studies suggest that the main reason for the enhanced noradrenaline-induced accumulation of IP3 in arteries from SHR rats is a reduced rate of dephosphorylation of both IP3 and inositol bisphosphate (IP2) rather than a greater formation of IP3 from PPIs.6. This enhanced accumulation of IP3 may result in an increased calcium mobilisation accounting for the increased contractility to noradrenaline of tail arteries from SHR as compared with those from WKY rats.

摘要

通过测量正常血压（WKY）大鼠和自发性高血压（SHR）大鼠尾动脉中肌醇磷酸（IPs）的积累，研究了去甲肾上腺素对多磷酸肌醇（PPI）分解的影响。2. 去甲肾上腺素（10⁻⁷ - 10⁻³ M）引起WKY和SHR大鼠中总IP积累呈浓度依赖性增加，但未检测到两组之间有显著差异。3. 相比之下，构成总IP的各个IP的积累存在显著差异。在每个有效去甲肾上腺素浓度下，与WKY大鼠组织相比，SHR大鼠组织中去甲肾上腺素刺激的肌醇三磷酸（IP3）积累显著更高。这与肌醇单磷酸（IP1）积累的相应减少相平行，这与两组之间去甲肾上腺素刺激的总IP积累缺乏显著差异一致。4. 在时间进程研究中，与WKY大鼠相比，在添加儿茶酚胺后的最早时间点，无论有无LiCl（10 mM），SHR大鼠中去甲肾上腺素诱导的IP3积累均增强。在存在LiCl（10 mM）的情况下，未观察到SHR和WKY大鼠之间去甲肾上腺素诱发的总IP积累有显著差异；在不存在LiCl的情况下，在所有研究时间点，去甲肾上腺素诱发的SHR大鼠总IP积累均高于WKY大鼠。5. 这些研究表明，SHR大鼠动脉中去甲肾上腺素诱导的IP3积累增强的主要原因是IP3和肌醇二磷酸（IP2）的去磷酸化速率降低，而不是PPI形成IP3的增加。6. 这种IP3积累的增强可能导致钙动员增加，这解释了与WKY大鼠相比，SHR大鼠尾动脉对去甲肾上腺素的收缩性增加。