Wuorela H, Arvola P, Kähönen M, Vapaatalo H, Pörsti I
Department of Biomedical Sciences, University of Tampere, Finland.
Pharmacol Toxicol. 1994 Mar;74(3):167-73. doi: 10.1111/j.1600-0773.1994.tb01094.x.
In order to further clarify differences between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats as well as the effects of ageing, vascular smooth muscle responses of mesenteric arterial rings and intracellular free calcium concentration ([Ca2+]i) in platelets and lymphocytes were studied in 20-week-old and 32-week-old animals. Arterial contractile responses induced by noradrenaline and potassium chloride were comparable in 20-week-old SHR and WKY rats, whereas at 32 weeks of age maximal contractile force generation to both of these agents was clearly lower in SHR. In both age groups the calcium entry blocker nifedipine was more effective in inhibiting potassium chloride-evoked responses in SHR than in WKY rats, and arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside, isoprenaline) mechanisms were more pronounced in WKY rats when compared with SHR. The ability of vascular smooth muscle cells to sequester calcium was evaluated by first depleting cellular calcium stores with maximal contractions to noradrenaline in calcium-free buffer, whereafter calcium was returned to the organ bath. After a 10 min. calcium loading period the arterial rings were rechallenged with noradrenaline. Both in 20-week-old and 32-week-old rats these responses were less marked in SHR than in WKY rats, suggesting reduced ability of smooth muscle cells to sequester calcium. In addition, platelets and lymphocytes were used as cell models to examine [Ca2+]i in the experimental groups by the fluorescent indicator quin-2. In these two cell types [Ca2+]i was higher in SHR than in WKY rats in both of the age groups studied.(ABSTRACT TRUNCATED AT 250 WORDS)
为了进一步阐明自发性高血压大鼠(SHR)与正常血压的Wistar-Kyoto(WKY)大鼠之间的差异以及衰老的影响,我们对20周龄和32周龄动物的肠系膜动脉环的血管平滑肌反应以及血小板和淋巴细胞中的细胞内游离钙浓度([Ca2+]i)进行了研究。去甲肾上腺素和氯化钾诱导的动脉收缩反应在20周龄的SHR和WKY大鼠中相当,而在32周龄时,SHR对这两种药物产生的最大收缩力明显较低。在两个年龄组中,钙通道阻滞剂硝苯地平在抑制SHR中氯化钾诱发的反应方面比WKY大鼠更有效,并且与SHR相比,WKY大鼠中依赖内皮(乙酰胆碱)和不依赖内皮(硝普钠、异丙肾上腺素)机制的动脉舒张反应更明显。通过在无钙缓冲液中用去甲肾上腺素进行最大收缩来耗尽细胞钙储备,然后将钙重新加入器官浴中,评估血管平滑肌细胞隔离钙的能力。在10分钟的钙加载期后,用去甲肾上腺素再次刺激动脉环。在20周龄和32周龄的大鼠中,SHR的这些反应均不如WKY大鼠明显,表明平滑肌细胞隔离钙的能力降低。此外,使用血小板和淋巴细胞作为细胞模型,通过荧光指示剂quin-2检测实验组中的[Ca2+]i。在研究的两个年龄组中,这两种细胞类型中SHR的[Ca2+]i均高于WKY大鼠。(摘要截断于250字)