ANTIHYPERTENSIVE ACTIONS OF ANGIOTENSIN-(1-7) IN SPONTANEOUSLY HYPERTENSIVE RATS
ANTIHYPERTENSIVE ACTIONS OF ANGIOTENSIN-(1-7) IN SPONTANEOUSLY HYPERTENSIVE RATS
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DOI：
10.1152/ajpheart.1995.269.1.h313
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发表时间：
1995-07-01
影响因子：
4.8
通讯作者：
DIZ, DI
中科院分区：
文献类型：
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作者：
BENTER, IF;FERRARIO, CM;DIZ, DI
血管紧张素-(1-7)[Ang-(1-7)]可能拮抗血管紧张素II(Ang II)的血管收缩作用，促使研究七肽对维持自发性高血压大鼠(SHR)血压升高的作用。Ang-(1-7)(24微克Kg(-1)。H(-1))给13周龄SHR(n=)、Wistar-京都(WKY)(n=50)和SpragueDawley(SD，n=18)大鼠颈静脉注入渗透压微泵2wk。分别于给药后第2、7、12天测定血压、水电解质平衡、血浆加压素、尿中前列腺素E(2)和6-酮-前列腺素F-1α(8-keto-PGF(1α))排泄量。在自发性高血压大鼠，Ang-(1-7)引起血浆加压素浓度持续显著降低，这与开始输注后第2天尿前列腺素E(2)和6-酮-PGF(1α)排泄量增加有关。SHR大鼠在输注后前3天出现上述变化，但WKY或SD大鼠未出现上述变化。动脉压的直接测量证实了Ang-(1-7)在治疗后第2天对SHR的收缩压的降低作用，并在第7天和第12天恢复血压。这些发现以及我们先前证明Ang-(1-7)在完整动物中是一种活性降压肽，表明在这种实验性高血压的遗传形式中，Ang-(1-7)可能作为一种对抗Ang II的血流动力学作用的血管降压系统发挥重要作用。
Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor actions of angiotensin II (ANG II) prompted an investigation of the effects of the heptapeptide on the maintenance of elevated blood pressure in spontaneously hypertensive rats (SHR). ANG-(1-7) (24 mu g . kg(-1). h(-1)) was infused into the jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague-Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood pressure, fluid and electrolyte balance, plasma vasopressin, and urinary excretion of prostaglandin E(2) and 6-ketoprostaglandin F-1 alpha (8-keto-PGF(1 alpha)) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7) caused a sustained and significant reduction in plasma vasopressin concentration that was associated with an increase in urinary prostaglandin E(2) and 6-keto-PGF(1 alpha) excretion at day 2 after the commencement of the infusion. These changes were accompanied by diuresis and natriuresis during the first 3 days of infusion in SHR but not in WKY or SD rats. Direct measurements of arterial pressure confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2 of treatment with a restoration of the pressure by days 7 and 12. These findings, along with our previous demonstration that ANG-(1-7) is an active depressor peptide in the intact animal, suggest that ANG-(1-7) may play a significant role as a vasodepressor system opposing the hemodynamic actions of ANG II in this genetic form of experimental hypertension.