β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats.
β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats.
复制标题
DOI：
10.3389/fneur.2014.00051
复制
发表时间：
2014
影响因子：
3.4
通讯作者：
Berg T
中科院分区：
文献类型：
--
作者：
Berg T
突触前β-肾上腺素受体促进外周去甲肾上腺素释放，据信仅涉及β2-亚型。然而，β1-选择性阻滞剂是治疗高血压最常用的β-阻滞剂。在此，作者检验了β1AR 可能作为突触前促进释放的自身受体发挥作用的假设。由于 β1AR 阻滞剂是在心肌梗塞期间注射的，因此还研究了它们对急性去甲肾上腺素释放的心血管反应的影响。通过一种新建立的方法，利用酪胺刺激的去甲肾上腺素转运蛋白（NET）释放，在正常血压和自发性高血压大鼠中研究了儿茶酚胺释放的突触前控制。在两种菌株中，β1AR 选择性拮抗剂（CGP20712A、阿替洛尔、美托洛尔）减少去甲肾上腺素溢出至血浆的效果与β2AR 选择性（ICI-118551）和 β1+2AR（纳多洛尔）拮抗剂相同。两种拮抗剂均不降低肾上腺素分泌。阿替洛尔不穿过血脑屏障，可减少肾上腺切除术 (AdrX)、AdrX + 神经节阻滞、氯沙坦或肾切除术后去甲肾上腺素的溢出。阿替洛尔和美托洛尔降低静息心脏工作负荷。在酪胺刺激的去甲肾上腺素释放过程中，它们对工作负荷几乎没有影响，并且增加了总外周血管阻力的短暂上升，特别是与氯沙坦联合使用阿替洛尔时。总之，β1AR 与 β2AR 一样，刺激去甲肾上腺素，但不刺激肾上腺素释放，与肾上腺儿茶酚胺、神经节传递或肾素释放/血管紧张素 AT1 受体激活无关。因此，β1AR 充当外周、突触前、促进自身受体。与酪胺一样，缺氧可能会诱导 NET 介导的释放。注射β1AR阻滞剂，特别是阿替洛尔与氯沙坦联合后观察到的酪胺诱导的血管收缩增强，可能会阻碍器官灌注，并且可能在心肌梗死等缺氧情况下具有临床意义。
Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.
登录
查看更多内容
影响因子：
3.4
作者：
Berg T;Jensen J
通讯作者：
Jensen J
影响因子：
7.3
作者：
MAJEWSKI, H;RAND, MJ;TUNG, LH
通讯作者：
TUNG, LH
影响因子：
3.2
作者：
Jezova, D;Ochedalski, T;Aguilera, G
通讯作者：
Aguilera, G
影响因子：
3
作者：
Esler, M;Kaye, D
通讯作者：
Kaye, D
影响因子：
7.3
作者：
ADLERGRASCHINSK.E;LANGER, SZ
通讯作者：
LANGER, SZ