Westfall Thomas C, Macarthur Heather, Byku Mirnela, Yang Chun-Lian, Murray Jessica
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Adv Pharmacol. 2013;68:115-39. doi: 10.1016/B978-0-12-411512-5.00006-3.
Work from our laboratory has established that angiotensin II (Ang II) produces a greater enhancement of the nerve stimulation (NS)-induced release (overflow) of both norepinephrine (NE) and neuropeptide Y (NPY) and a greater increase in perfusion pressure of the mesenteric arterial bed obtained from the spontaneously hypertensive rat (SHR) compared to age-matched Wistar-Kyoto (WKY) or Sprague-Dawley rats. The enhancement of NS-induced NPY release was blocked by the AT1 receptor antagonist EMD 66684 and the AT2 receptor antagonist PD 123319. Both captopril and EMD 66684 decreased NPY and NE overflow from SHR mesenteric beds, suggesting an endogenous renin-angiotensin system (RAS) is active in the mesenteric artery. We also observed that the recently discovered new arm of the RAS, namely, angiotensin (1-7) (Ang-(1-7)), attenuated the NS-induced increase in NE and NPY release and the accompanied increased perfusion pressure. These inhibitory effects were greater in blood vessels obtained from SHR compared to WKY. We suggest that inhibition of sympathetic neurotransmission contributes to the mechanism(s) by which Ang-(1-7) acts to inhibit the vasoconstrictor effect of Ang II. Administration of the MAS receptor antagonist D-Ala(7)Ang-(1-7) attenuated the decrease in both NE and NPY release due to Ang-(1-7) administration. The AT2 receptor antagonist PD 123391 attenuated the effect of Ang-(1-7) on NE release without affecting the decrease in NPY release. We observed a shift in the balance between Ang II and Ang-(1-7) levels in the SHR with an increase in Ang II and a decrease in Ang-(1-7) in the blood and mesenteric artery. This appears to be due to an increase in angiotensin-converting enzyme (ACE) in the mesenteric artery of the SHR.
我们实验室的研究已证实，与年龄匹配的Wistar-Kyoto（WKY）大鼠或Sprague-Dawley大鼠相比，血管紧张素II（Ang II）能更大程度地增强神经刺激（NS）诱导的去甲肾上腺素（NE）和神经肽Y（NPY）释放（溢出），并使自发性高血压大鼠（SHR）肠系膜动脉床的灌注压有更大升高。NS诱导的NPY释放增强被AT1受体拮抗剂EMD 66684和AT2受体拮抗剂PD 123319阻断。卡托普利和EMD 66684均降低了SHR肠系膜床中NPY和NE的溢出，提示内源性肾素-血管紧张素系统（RAS）在肠系膜动脉中具有活性。我们还观察到，RAS最近发现的新分支，即血管紧张素（1-7）（Ang-(1-7)），减弱了NS诱导的NE和NPY释放增加以及伴随的灌注压升高。与WKY大鼠相比，这些抑制作用在SHR的血管中更明显。我们认为，抑制交感神经传递是Ang-(1-7)发挥作用抑制Ang II血管收缩效应的机制之一。给予MAS受体拮抗剂D-Ala(7)Ang-(1-7)减弱了因给予Ang-(1-7)而导致的NE和NPY释放减少。AT2受体拮抗剂PD 123391减弱了Ang-(1-7)对NE释放的作用，但不影响NPY释放的减少。我们观察到SHR中Ang II和Ang-(1-7)水平的平衡发生了变化——血液和肠系膜动脉中Ang II增加而Ang-(1-7)减少。这似乎是由于SHR肠系膜动脉中血管紧张素转换酶（ACE）增加所致。
