Cerebroventricular injection of angiotensin II antagonist: effects on blood pressure responses to central and systemic angiotensin II.
Cerebroventricular injection of angiotensin II antagonist: effects on blood pressure responses to central and systemic angiotensin II.
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发表时间：
1995-05
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通讯作者：
V. J. Gorbea-Oppliger;G. Fink
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作者：
V. J. Gorbea-Oppliger;G. Fink
循环血管紧张素II（ANG II）具有几种生理效应，这些效应是由肽与脑中的AT 1受体相互作用引起的。我们的目的是确定选择性药物阻断脑AT 1受体是否会逆转慢性低剂量ANG II诱导的高血压。雄性Sprague-Dawley大鼠用慢性留置动脉和静脉导管和侧脑室（i. c. v.）插管。所有大鼠均接受ANG II静脉注射，剂量为4 ng.min-1，持续15天。在ANG II输注的第2、7和12天，静脉推注一种AT 1受体拮抗剂，氯沙坦的活性代谢物，EXP 3174（1微克溶于2微升盐水，i. c. v.; n = 5）或赋形剂（2微升盐水; n = 2）施用到脑脊液中。在注射后的许多时间点测量平均动脉压和心率。尽管初步实验中使用的EXP 3174剂量显示可阻断对i. c. v. ANG II的反应，但该治疗并未降低慢性ANG II-高血压患者的MAP。这些结果表明，ANG II-高血压不涉及脑AT 1受体，或者i. c. v. EXP 3174可能无法进入循环ANG II产生高血压的脑部位。为了测试后一种可能性，将ANG II微量注射到麻醉大鼠的最后区。最后区是循环血管紧张素II可影响动脉压调节的几个室周器官之一。（250字处删节）
Circulating angiotensin II (ANG II) has several physiological effects that result from interaction of the peptide with AT1 receptors in the brain. Our purpose was to determine if selective pharmacological blockade of brain AT1 receptors would reverse chronic low-dose ANG II-induced hypertension. Male Sprague-Dawley rats were instrumented with chronic indwelling arterial and venous catheters and a lateral intracerebroventricular (i.c.v.) cannula. All rats received ANG II i.v. for 15 days at a dose of 4 ng.min-1. On days 2, 7 and 12 of the ANG II infusion a bolus of an AT1 receptor antagonist, the active metabolite of losartan, EXP 3174 (1 microgram in 2 microliters of saline, i.c.v.; n = 5) or vehicle (2 microliters of saline; n = 2) was administered into the cerebrospinal fluid. Mean arterial pressure and heart rate were measured at numerous time points after this injection. Although the dose of EXP 3174 used in preliminary experiments was shown to block the responses to i.c.v. ANG II this treatment did not lower MAP in chronic ANG II-hypertension. These results suggested that either ANG II-hypertension does not involve brain AT1 receptors, or that i.c.v. EXP 3174 may not gain access to brain sites at which circulating ANG II acts to produce hypertension. To test this latter possibility ANG II was microinjected into the area postrema of anesthetized rats. The area postrema is one of several circumventricular organs at which circulating ANG II may act to influence arterial pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS)