NEUROHUMORAL CONTRIBUTIONS TO CHRONIC ANGIOTENSIN-INDUCED HYPERTENSION
NEUROHUMORAL CONTRIBUTIONS TO CHRONIC ANGIOTENSIN-INDUCED HYPERTENSION
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DOI：
10.1152/ajpheart.1986.250.1.h52
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发表时间：
1986-01-01
影响因子：
--
通讯作者：
FINK, GD
中科院分区：
文献类型：
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作者：
BRUNER, CA;FINK, GD
血管紧张素II（ANG II）的中枢升压作用与几种实验性高血压的发病机制有关。因此，本研究旨在研究慢性脑室内（ICV）输注ANG II选择性刺激脑ANG II受体导致高血压的机制。具体地，在通过5- 7天ICV ANG II输注（6 μ g/h）而造成高血压的大鼠中研究了交感神经系统的作用、加压素的升压作用和作用性ANG II的直接血管收缩作用。大鼠长期使用留置动脉和静脉导管和侧脑室插管。在ICV ANG II输注期间急性静脉输注竞争性ANG受体拮抗剂[SAr 1-Ala 8]ANG II导致动脉压中度降低，表明血源性ANG II增加可能是ICV ANG II高血压反应的一小部分。交感神经系统的激活似乎是动脉压升高的主要原因，因为急性神经节阻滞和组合的α-和β-肾上腺素能阻滞剂在慢性ICV ANG II输注致高血压大鼠中产生的降压反应比正常血压大鼠更大。此外，外周交感神经切除术延迟高血压的发展。静脉注射血管加压素受体的特异性拮抗剂不会引起慢性ICV ANG II输注高血压大鼠的降压反应。这些研究表明，涉及急性ICV ANG II注射的升压反应的主要机制，即加压素释放，似乎不会导致慢性ICV输注ANG II产生的高血压。相反，这种形式的高血压的主要特征是交感血管收缩张力增加，并可能通过ANG II循环水平小幅增加激活的机制。
A central pressor effect of angiotensin II (ANG II) has been implicated in the pathogenesis of several forms of experimental hypertension. Therefore, the present studies were designed to investigate mechanisms that contribute to hypertension resulting from selective stimulation of brain ANG II receptors by chronic intracerebroventricular (ICV) infusion of ANG II. Specifically, the role of the sympathetic nervous system, the pressor actions of vasopressin, and the direct vasoconstrictor effect of actions-borne ANG II were investigated in rats made hyertensive by 5- to 7-day ICV ANG II infusions (6 .mu.g/h). Rats were chronically instrumented with indwelling arterial and venous catheters and a lateral cerebral ventricular cannula. Acute intravenous infusion of the competitive ANG receptor antagonist [SAr1-Ala8]ANG II during the period of ICV ANG II infusion resulted in a moderate decrease in arterial pressure, indicating that an increase in blood-borne ANG II may account for a small component of the hypertensive response to ICV ANG II. Activation of the sympathetic nervous system appeared to be the major contributor to the elevated arterial pressure, since acute ganglionic blockade and combined .alpha.- and .beta.-adrenergic blockade produced greater depressor responses in rats made hypertensive with chronic ICV ANG II infusion than in normotensive rats. Furthermore, peripheral sympathectomy delayed hypertension development. Intravenous administration of a specific antagonist of the vascular vasopressin receptor did not cause a depressor response in rats made hypertensive with chronic ICV ANG II infusions. These studies demonstrate that a major mechanism involved in the pressor response to acute ICV ANG II injections, namely vasopressin release, does not appear to contribute to hypertension produced by chronic ICV infusions of ANG II. Rather, this form of hypertension is characterized predominantly by an increase in sympathetic vasoconstrictor tone and possibly by a mechanism activated by a small increase in circulating levels of ANG II.