Shimizu Fumihiro, Kasai Toshihiro, Takamata Akira
Department of Environmental Health, Nara Women's Univesity, Kitauoya Nishimachi, Nara 630-8506, Japan.
J Appl Physiol (1985). 2009 Jun;106(6):1943-8. doi: 10.1152/japplphysiol.90516.2008. Epub 2009 Apr 9.
The purpose of this study was to evaluate the involvement of central angiotensin II (ANG II) and ANG II type 1 (AT(1)) receptors in systemic release of arginine vasopressin (AVP) and blood pressure regulation during endotoxemia. LPS (150 microg/kg) was injected intravenously 30 min after intracerebroventricular (icv) losartan (50 microg), an AT(1) receptor antagonist, or subcutaneous (sc) captopril (50 mg/kg), an angiotensin-converting enzyme inhibitor. Rats with icv and sc saline injections served as control. LPS administration increased plasma AVP concentration from 2.1 +/- 0.2 to 15.2 +/- 2.5 pg/ml (60 min after LPS injection) without significant changes in plasma osmolality or hematocrit. LPS-induced AVP secretion was significantly attenuated by pretreatment with icv losartan (2.3 +/- 0.5 to 3.7 +/- 0.5 pg/ml) but was not attenuated after peripheral captopril treatment (2.2 +/- 0.6 to 17.6 +/- 4.2 pg/ml). LPS administration significantly decreased systolic blood pressure (SBP) by 22.7 +/- 5.4 mmHg after intravenous LPS injection in icv losartan-treated rats, while SBP remained unchanged in vehicle-treated or sc captopril-treated rats by intravenous LPS. These results indicate that central AT(1) receptors, not responsive to peripheral ANG II, play an important role in systemic AVP secretion and maintenance of blood pressure during endotoxemia.
本研究的目的是评估内毒素血症期间中枢血管紧张素II(ANG II)和1型血管紧张素II(AT(1))受体在精氨酸加压素(AVP)的全身释放及血压调节中的作用。在脑室内(icv)注射AT(1)受体拮抗剂氯沙坦(50微克)或皮下(sc)注射血管紧张素转换酶抑制剂卡托普利(50毫克/千克)30分钟后,静脉注射脂多糖(LPS,150微克/千克)。icv和sc注射生理盐水的大鼠作为对照。给予LPS后,血浆AVP浓度从2.1±0.2皮克/毫升增加至15.2±2.5皮克/毫升(注射LPS后60分钟),而血浆渗透压或血细胞比容无显著变化。LPS诱导的AVP分泌经icv氯沙坦预处理后显著减弱(从2.3±0.5皮克/毫升降至3.7±0.5皮克/毫升),但外周给予卡托普利后未减弱(从2.2±0.6皮克/毫升升至17.6±4.2皮克/毫升)。在icv氯沙坦处理的大鼠中,静脉注射LPS后,LPS给药使收缩压(SBP)显著降低22.7±5.4毫米汞柱,而在静脉注射LPS时,在溶剂处理或sc卡托普利处理的大鼠中SBP保持不变。这些结果表明,对内周ANG II无反应的中枢AT(1)受体在内毒素血症期间全身AVP分泌和血压维持中起重要作用。