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注射于自发性高血压大鼠内侧前额叶皮质的L-谷氨酸的心血管效应。

Cardiovascular effects of L-glutamate injected in the medial prefrontal cortex of spontaneously hypertensive rats.

作者信息

Resstel Leonardo B M, Corrêa Fernando M A

机构信息

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.

出版信息

Eur J Pharmacol. 2008 Feb 12;580(3):372-9. doi: 10.1016/j.ejphar.2007.11.020. Epub 2007 Nov 23.

Abstract

We have previously reported that l-glutamate (L-glu) injected into the ventral portion of medial prefrontal cortex (vMPFC) of unanesthetized normotensive Wistar rats elicited cardiovascular responses. In the present study we investigated whether the spontaneously hypertensive rat (SHR) exhibit abnormal cardiovascular responses after L-glu microinjection in the vMPFC. Microinjections of L-glu (3, 9, 27, 81 or 150 nmol/200 nl) caused long-lasting dose-related depressor and bradycardiac responses in unanesthetized SHR (n=6, each dose). Pressor and tachycardiac responses were evoked after the injection of 81 nmol of L-glu in the vMPFC of normotensive Wistar rats (n=6). Systemic pretreatment with the beta1-adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.) had no effect on L-glu cardiovascular responses evoked in the SHR (n=5). However, the treatment with the muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) blocked the bradycardiac response to L-glu, without significant effects on depressor response evoked by L-glu in the SHR (n=5). These results indicate that the bradycardiac response to the injection of L-glu injection in the vMPFC is due to activation of the parasympathetic system and not to inhibition of the cardiac sympathetic input. In conclusion, results indicate opposite cardiovascular responses when L-glu was microinjected in the vMPFC of unanesthetized SHR or normotensive. The bradycardiac response observed in the SHR was due to parasympathetic activation and was not affected by pharmacological blockade of the cardiac sympathetic output.

摘要

我们之前报道过,向未麻醉的正常血压Wistar大鼠的内侧前额叶皮质腹侧部(vMPFC)注射L-谷氨酸(L-glu)会引发心血管反应。在本研究中,我们调查了自发性高血压大鼠(SHR)在vMPFC中注射L-glu后是否表现出异常的心血管反应。向未麻醉的SHR(n = 6,每组剂量)微量注射L-glu(3、9、27、81或150 nmol/200 nl)会引起持续的剂量相关的降压和心动过缓反应。向正常血压Wistar大鼠(n = 6)的vMPFC注射81 nmol的L-glu后会诱发升压和心动过速反应。用β1-肾上腺素能受体拮抗剂阿替洛尔(1.5 mg/kg,静脉注射)进行全身预处理对SHR中诱发的L-glu心血管反应没有影响(n = 5)。然而,用毒蕈碱拮抗剂甲基溴东莨菪碱(1 mg/kg,静脉注射)治疗可阻断对L-glu的心动过缓反应,而对SHR中L-glu诱发的降压反应没有显著影响(n = 5)。这些结果表明,在vMPFC中注射L-glu引起的心动过缓反应是由于副交感神经系统的激活,而不是由于心脏交感神经输入的抑制。总之,结果表明,当在未麻醉的SHR或正常血压大鼠的vMPFC中微量注射L-glu时,会出现相反的心血管反应。在SHR中观察到的心动过缓反应是由于副交感神经激活,并且不受心脏交感神经输出的药理学阻断的影响。

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