Ito S, Sved A F
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15620, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2961-6. doi: 10.1152/ajpheart.2000.279.6.H2961.
Injection of sarthran, an angiotensin receptor antagonist, bilaterally into the rostral ventrolateral medulla (RVLM) of alpha-chloralose-anesthetized rats decreases arterial pressure (AP) to the same extent as total autonomic blockade. This response is not reproduced by selective AT(1) antagonists. To examine the pharmacological profile of the response elicited by [Sar(1), Thr(8)]ANG II (sarthran), the ability of angiotensin analogs to inhibit the effect of sarthran injected into the RVLM was tested. Coinjection of angiotensin II (ANG II) prevented the sarthran-evoked decrease in AP, but this action of ANG II was markedly attenuated by pretreatment of the RVLM with the aminopeptidase inhibitor amastatin. Coinjection of ANG(3-8) or a selective agonist of AT(4) receptors prevented the effect of sarthran injected into the RVLM. ANG(1-7) was also able to prevent the effect of sarthran. None of the angiotensin fragments tested substantially altered blood pressure when injected alone into the RVLM. These results suggest that the depressor action of sarthran injected into the RVLM is not dependent on ANG II receptors, though the nature of the site or sites of action of sarthran within the RVLM remains uncertain.
将血管紧张素受体拮抗剂萨尔坦双侧注射到α-氯醛糖麻醉大鼠的延髓头端腹外侧区（RVLM），可使动脉血压（AP）降低，其程度与完全自主神经阻滞相同。选择性AT(1)拮抗剂无法重现这种反应。为了研究[Sar(1), Thr(8)]ANG II（萨尔坦）引发的反应的药理学特征，测试了血管紧张素类似物抑制注射到RVLM的萨尔坦作用的能力。同时注射血管紧张素II（ANG II）可防止萨尔坦引起的AP降低，但用氨肽酶抑制剂阿马astatin预处理RVLM后，ANG II的这种作用明显减弱。同时注射ANG(3 - 8)或AT(4)受体的选择性激动剂可防止注射到RVLM的萨尔坦的作用。ANG(1 - 7)也能够防止萨尔坦的作用。单独注射到RVLM时，所测试的血管紧张素片段均未显著改变血压。这些结果表明，注射到RVLM的萨尔坦的降压作用不依赖于ANG II受体，尽管萨尔坦在RVLM内的作用位点的性质仍不确定。
