Activation by CGP 12177 and cyanopindolol of the human and rat low-'/> Positive inotropic and lusitropic effects mediated via the low-affinity state of β1-adrenoceptors in pithed rats
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首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Positive inotropic and lusitropic effects mediated via the low-affinity state of β1-adrenoceptors in pithed rats
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Positive inotropic and lusitropic effects mediated via the low-affinity state of β1-adrenoceptors in pithed rats

机译：β1肾上腺素受体低亲和力状态介导的正性肌力和促智作用

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class="enumerated" style="list-style-type:decimal">Activation by CGP 12177 and cyanopindolol of the human and rat low-affinity state of β1-adrenoceptors increases frequency and contractile force and hastens relaxation in isolated cardiac tissues, and probably relaxes isolated vessels. In order to identify the positive inotropic, positive lusitropic and vasodilator effects of both agonists also in vivo, we have determined their effects on the left ventricular systolic pressure (LVSP), the rate of intraventricular pressure rise (+dP dt−1max) and decline (−dP dt−1max), the diastolic blood pressure (DBP) and the mesenteric blood flow (MBF) in pithed and vagotomized rats.CGP 12177 (0.1–100 nmol kg−1) and cyanopindolol (1–1000 nmol kg−1) dose-dependently enhanced all cardiac parameters. The nonselective β-adrenoceptor antagonist bupranolol 10 μmol kg−1 diminished the CGP 12177 (100 nmol kg−1)-stimulated increases in LVSP from 26.3±8.2 to 13.1±1.8 mmHg (P<0.05), +dP dt−1max from 5287±290 to 2439±296 mmHg s−1 (P<0.001) and −dP dt−1max from −3836±301 to −2187±443 mmHg s−1 (P<0.05), respectively. The β1-adrenoceptor antagonist CGP 20712A 10 μmol kg−1 (known to block the low-affinity state of β1-adrenoceptors at high doses) inhibited increases in ±dP dt−1max elicited by the highest dose of CGP 12177.The highest doses of CGP 12177 and cyanopindolol increased DBP by about 10 mmHg and MBF by 1.4±0.3 and 0.6±0.3 ml min−1, respectively. The vascular effects of CGP 12177 were not affected by bupranolol and CGP 20712A.In conclusion, activation of the low-affinity state of β1-adrenoceptors by CGP 12177 and cyanopindolol in pithed rats causes a positive inotropic and lusitropic effect. By contrast, the vascular effects of CGP 12177 and cyanopindolol are not mediated by these receptors and have only marginal influence under in vivo conditions.
机译：class =“ enumerated” style =“ list-style-type：decimal”> <！-list-behavior =枚举前缀-word = mark-type = decimal max-label-size = 0-> CGP 12177和氰基吲哚洛尔对人和大鼠低亲和力状态的β1-肾上腺素受体的激活增加了频率和收缩力，并加速了离体心脏组织的松弛，并可能使离体血管松弛。为了确定两种激动剂在体内的正性肌力，正性肌力和血管舒张剂的作用，我们确定了它们对左心室收缩压（LVSP），心室内压上升率（+ dP dt -1 max）和下降（-dP dt -1 max），经去皮和迷走神经切断的大鼠的舒张压（DBP）和肠系膜血流量（MBF）。 < li> CGP 12177（0.1–100 nmol kg -1 ）和氰基吲哚洛尔（1–1000 nmol kg -1 ）剂量依赖性地改善所有心脏参数。非选择性β-肾上腺素受体拮抗剂普萘洛尔10μmolkg −1 减少了CGP 12177（100 nmol kg -1 ）刺激的LVSP从26.3±8.2升高至13.1±1.8 mmHg（P <0.05），+ dP dt -1 max从5287±290到2439±296 mmHg s -1 （P <0.001）和-dP dt −1 max从−3836±301到−2187±443 mmHg s -1 （P <0.05）。 β1-肾上腺素受体拮抗剂CGP 20712A 10 μ mol kg −1 （已知在高水平时会阻断β 1-肾上腺素受体的低亲和力状态剂量）抑制了CGP 12177最高剂量引起的±d P d t -1 max的增加。 CGP 12177和氰基吲哚洛尔的最高剂量分别使DBP升高约10 mmHg，MBF升高1.4±0.3和0.6±0.3±ml min -1 。丁丙诺醇和CGP 20712A不会影响CGP 12177的血管作用。 最后，CGP 12177和氰基吲哚洛尔激活了β 1-肾上腺素受体的低亲和力状态。脱髓鞘的大鼠会产生正性的肌力和正性肌力作用。相比之下，CGP 12177和氰基吲哚的血管作用不是由这些受体介导的，而在体内条件下只有很小的影响。

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