Evered M D, Siddiqui S H, Kenyon P J
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Brain Res Bull. 1989 Oct-Nov;23(4-5):289-92. doi: 10.1016/0361-9230(89)90211-6.
Investigators using intracerebroventricular (ICV) injections of competitive antagonists of angiotensin II (Ang II) to study thirst usually select doses sufficient to block drinking to IV Ang II. We questioned whether this test truly indicates the dose needed under physiological conditions when Ang II-induced hypertension, which inhibits thirst, is not present. Rats were prepared with chronic venous and ICV cannulas, plus femoral arterial cannulas in those used to measure arterial pressure. Captopril (100 mg/kg SC) was given before all experiments to block endogenous Ang II production. The test dose of Ang II, 50 ng/kg/min IV for 1 hr, increased water intake and arterial pressure. We selected an ICV dose of saralasin (Sar1Ala8Ang II), 4 micrograms bolus and 4 micrograms/hr for 75 min, that did not stimulate drinking itself and completely blocked drinking to IV Ang II. This dose of saralasin only partially (45%) reduced drinking to the same dose of Ang II IV when arterial pressure was lowered by giving the vasodilator diazoxide (15 mg/kg IV). Diazoxide itself did not stimulate drinking. These results support our concern that the criterion normally used to select ICV doses of Ang II antagonists probably underestimates the amount needed to inhibit angiotensinergic drinking in hypovolemic or hypotensive animals.
研究人员使用脑室内（ICV）注射血管紧张素II（Ang II）竞争性拮抗剂来研究口渴时，通常会选择足以阻断静脉注射Ang II引起的饮水的剂量。我们质疑，当不存在抑制口渴的Ang II诱导的高血压时，该测试是否真的能表明生理条件下所需的剂量。给大鼠植入慢性静脉和ICV插管，用于测量动脉血压的大鼠还植入股动脉插管。在所有实验前给予卡托普利（100mg/kg皮下注射）以阻断内源性Ang II的产生。Ang II的测试剂量为50ng/kg/min静脉注射1小时，可增加水摄入量和动脉血压。我们选择了ICV剂量的沙拉新（Sar1Ala8Ang II），推注4微克，每小时4微克，持续75分钟，该剂量本身不会刺激饮水，并且能完全阻断静脉注射Ang II引起的饮水。当通过静脉注射血管扩张剂二氮嗪（15mg/kg）降低动脉血压时，该剂量的沙拉新仅部分（45%）减少了对相同剂量静脉注射Ang II的饮水。二氮嗪本身不会刺激饮水。这些结果支持了我们的担忧，即通常用于选择ICV剂量的Ang II拮抗剂的标准可能低估了低血容量或低血压动物抑制血管紧张素能性饮水所需的量。
