Angiotensin-(1-12) in the rostral ventrolateral medullary pressor area of the rat elicits sympathoexcitatory responses
Angiotensin-(1-12) in the rostral ventrolateral medullary pressor area of the rat elicits sympathoexcitatory responses
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DOI：
10.1113/expphysiol.2012.067116
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发表时间：
2013-01-01
影响因子：
2.7
通讯作者：
Sapru, Hreday N.
中科院分区：
文献类型：
--
作者：
Arakawa, Hideki;Kawabe, Kazumi;Sapru, Hreday N.
延髓头端腹外侧加压区（RVLM）在心血管功能的调节中起重要作用。本研究假设RVLM可能是新发现的血管紧张素-（1-12）[Ang-（1 - 12）]的心血管作用部位之一。实验在麻醉、人工通气的成年雄性Wistar大鼠中进行。通过微量注射l-谷氨酸盐（5 mM）鉴定RVLM。所有显微注射到RVLM中的体积为100 nl。RVLM内微量注射Ang-（1-12）（0.1- 1.0mM）引起平均动脉压和心率的增加。最大心血管反应由0.5 mM Ang-（1-12）引起;该浓度用于所述的其他实验中。微量注射Ang-（1-12）可增加内脏神经活动。切断双侧迷走神经不改变对Ang-（1-12）的心动过速反应。RVLM内微量注射血管紧张素Ⅱ 1型受体（AT（1）R）拮抗剂（氯沙坦）可减弱Ang-（1-12）引起的心血管反应，而注射AT（2）R拮抗剂（PD 123319）则无此作用。联合抑制RVLM中的血管紧张素转换酶和糜酶可消除Ang-（1-12）诱导的反应。RVLM内可见血管紧张素-（1-12）免疫反应阳性细胞。血管紧张素Ⅱ 1型受体和苯乙醇胺-N-甲基转移酶存在于RVLM神经元逆行标记的Fluoro-Gold显微注射到中间外侧细胞柱的胸脊髓。下丘脑室旁核的血管紧张素-（1-12）阳性神经元不投射到RVLM。这些结果表明：（1）RVLM内微量注射Ang-（1-12）可引起平均动脉压、心率和内脏神经活动增加;（2）Ang-（1-12）转化为血管紧张素II需要血管紧张素转换酶和糜酶;（3）RVLM内AT（1）Rs而非AT（2）Rs介导Ang（1-12）诱导的反应。
The rostral ventrolateral medullary pressor area (RVLM) is known to be critical in the regulation of cardiovascular function. In this study, it was hypothesized that the RVLM may be one of the sites of cardiovascular actions of a newly discovered angiotensin, angiotensin-(1-12) [Ang-(1-12)]. Experiments were carried out in urethane-anaesthetized, artificially ventilated, adult male Wistar rats. The RVLM was identified by microinjections of l-glutamate (5 mM). The volume of all microinjections into the RVLM was 100 nl. Microinjections of Ang-(1-12) (0.1-1.0 mM) into the RVLM elicited increases in mean arterial pressure and heart rate. Maximal cardiovascular responses were elicited by 0.5 mM Ang-(1-12); this concentration was used in the other experiments described. Microinjections of Ang-(1-12) increased greater splanchnic nerve activity. The tachycardic responses to Ang-(1-12) were not altered by bilateral vagotomy. The cardiovascular responses elicited by Ang-(1-12) were attenuated by microinjections of an angiotensin II type 1 receptor (AT(1)R) antagonist (losartan), but not an AT(2)R antagonist (PD123319), into the RVLM. Combined inhibition of angiotensin-converting enzyme and chymase in the RVLM abolished Ang-(1-12)-induced responses. Angiotensin-(1-12)-immunoreactive cells were present in the RVLM. Angiotensin II type 1 receptors and phenylethanolamine-N-methyl-transferase were present in the RVLM neurons retrogradely labelled by microinjections of Fluoro-Gold into the intermediolateral cell column of the thoracic spinal cord. Angiotensin-(1-12)-containing neurons in the hypothalamic paraventricular nucleus did not project to the RVLM. These results indicated that: (1) microinjections of Ang-(1-12) into the RVLM elicited increases in mean arterial pressure, heart rate and greater splanchnic nerve activity; (2) both angiotensin-converting enzyme and chymase were needed to convert Ang-(1-12) into angiotensin II; and (3) AT(1)Rs, but not AT(2)Rs, in the RVLM mediated the Ang(1-12)-induced responses.