Grundt Alexander, Grundt Christina, Gorbey Stefan, Thomas Martin A, Lemmer Björn
Institute of Experimental and Clinical Pharmacology and Toxicology, Ruprecht-Karls-Universität of Heidelberg, Mannheim, Germany.
Physiol Behav. 2009 Jun 22;97(3-4):341-6. doi: 10.1016/j.physbeh.2009.02.029. Epub 2009 Mar 5.
The aim of our study was to investigate differences in restraint stress-response between normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) and the consequences for tail-cuff (TC) blood pressure measurements. We therefore radiotelemetrically collected cardiovascular data from WKY and SHR that underwent TC procedures and measured plasma norepinephrine (NE) and angiotensin II (ATII) levels as well as gene expression of the adrenal and hypothalamic tyrosine-hydroxylase, the rate-limiting enzyme in NE synthesis. Furthermore, we determined the effects of antihypertensive therapy using the beta(1)-receptor antagonist metoprolol, the alpha(1)-receptor antagonist doxazosin and the AT(1)-receptor antagonist telmisartan as mono- or combination therapies during the TC procedure. Results show that the TC procedure induced a stress reaction characterised by greatly increasing heart rate (HR) and blood pressure (BP) and elevating plasma norepinephrine and angiotensin II concentrations. Strain-dependent differences were found concerning stress reactions during rest (more pronounced effects) and activity of the two rat strains. In both strains, metoprolol inhibited the TC-induced increase in HR and doxazosin the TC-induced increase in BP. Telmisartan, in addition, reduced hypertension in SHR, slightly reduced the TC-induced increase of BP in SHR but had no effect in WKY. The cardiovascular data as well as those on NE, ATII and TH expression clearly show that SHR are less able to cope with stress-related mechanisms than the normotensive WKY. Since TC activates both the sympathetic as well as renin-angiotensin system this method is not appropriate to evaluate neither physiological nor drug-induced effects on BP and HR.
我们研究的目的是调查正常血压的Wistar Kyoto大鼠(WKY)和自发性高血压大鼠(SHR)之间在束缚应激反应上的差异以及对尾袖法(TC)测量血压的影响。因此,我们通过无线电遥测技术收集了接受TC操作的WKY和SHR的心血管数据,并测量了血浆去甲肾上腺素(NE)和血管紧张素II(ATII)水平以及肾上腺和下丘脑酪氨酸羟化酶(NE合成中的限速酶)的基因表达。此外,我们确定了在TC操作期间使用β1受体拮抗剂美托洛尔、α1受体拮抗剂多沙唑嗪和AT1受体拮抗剂替米沙坦作为单一疗法或联合疗法进行抗高血压治疗的效果。结果表明,TC操作引发了一种应激反应,其特征为心率(HR)和血压(BP)大幅升高以及血浆去甲肾上腺素和血管紧张素II浓度升高。在两种大鼠品系的静息期应激反应(影响更明显)和活动方面发现了品系依赖性差异。在两个品系中,美托洛尔抑制了TC诱导的HR升高,多沙唑嗪抑制了TC诱导的BP升高。此外,替米沙坦降低了SHR的高血压,略微降低了SHR中TC诱导的BP升高,但对WKY没有影响。心血管数据以及关于NE、ATII和TH表达的数据清楚地表明,与正常血压的WKY相比,SHR应对应激相关机制的能力较弱。由于TC激活了交感神经系统以及肾素 - 血管紧张素系统,因此该方法不适用于评估对BP和HR的生理影响或药物诱导的影响。