内皮素-1或NG-硝基-L-精氨酸甲酯给药后，人α-降钙素基因相关肽对清醒大鼠的血流动力学影响。
Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats.
作者信息
Gardiner S M, Compton A M, Kemp P A, Bennett T, Foulkes R, Hughes B
机构信息
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
出版信息
Br J Pharmacol. 1991 May;103(1):1256-62. doi: 10.1111/j.1476-5381.1991.tb12333.x.
1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of endothelin-1 or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of endothelin-1 (3 nmol kg-1 h-1) caused hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions. Co-infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) reduced the hypertension and abolished the hindquarters vasoconstriction caused by endothelin-1 but the renal and mesenteric vasoconstrictor actions of endothelin-1 were not affected. 3 Infusion of human alpha-CGRP (15 nmol kg-1 h-1) in the presence of endothelin-1 caused hypotension and hyperaemic vasodilatation in the hindquarters; the mesenteric vasoconstrictor effects of endothelin-1 were diminished, but there was only a transient reversal of the renal vasoconstrictor effects of endothelin-1. 4 Pretreatment with the non-peptide angiotensin II receptor antagonist, DuP 753 (10 mg kg-1), caused slight hypotension associated with renal, mesenteric and hindquarters vasodilatations, but DuP 753 did not affect responses to endothelin-1 infusion. However, under these conditions co-infusion of human alpha-CGRP (15 nmol kg-1 h-1) caused a sustained reversal of the renal vasoconstrictor effects of endothelin-1. 5 These results indicate that the failure of human alpha-CGRP to cause sustained reversal of the renal vasoconstrictor effects of endothelin-1 in the absence of DuP 753 was due to activation of the reninangiotensin system (possibly as a consequence of the hypotension). 6. In the second experiment, L-NAME (l0mgkg-1) caused renal, mesenteric and hindquarters vasoconstrictions similar to those seen in the presence of endothelin-1. However, the renal vasoconstrictor effects of L-NAME were reversed completely by human alpha-CGRP (l5nmolkg- h-1), even though the latter caused hypotension comparable to that seen in the presence of endothelin-1. These results are consistent with a lack of functional activation of the renin-angiotensin system by human alpha-CGRP in the presence of L-NAME. 7. The vasoconstrictor effects of L-NAME on the hindquarters were completely reversed by infusion of human alpha-CGRP, but hindquarters flow and vascular conductance did not rise above baseline levels. Hence these results indicate the hindquarters hyperaemic vasodilator effects of human alpha-CGRP seen in the presence of endothelin-1 were contributed to by nitric oxide-mediated mechanisms.
我们在清醒、长期植入仪器的朗·埃文斯大鼠中，研究了给予内皮素 -1 或一氧化氮生成抑制剂 NG - 硝基 -L - 精氨酸甲酯（L - NAME）后，人α - 降钙素基因相关肽（CGRP）的外周血流动力学效应。
输注内皮素 -1（3 nmol·kg⁻¹·h⁻¹）导致高血压、心动过缓以及肾、肠系膜和后肢血管收缩。共同输注人α - CGRP（1.5 nmol·kg⁻¹·h⁻¹）可降低高血压，并消除内皮素 -1 引起的后肢血管收缩，但内皮素 -1 的肾和肠系膜血管收缩作用未受影响。
在存在内皮素 -1 的情况下输注人α - CGRP（15 nmol·kg⁻¹·h⁻¹）导致低血压和后肢充血性血管扩张；内皮素 -1 的肠系膜血管收缩作用减弱，但内皮素 -1 的肾血管收缩作用仅出现短暂逆转。
用非肽类血管紧张素 II 受体拮抗剂 DuP 753（10 mg·kg⁻¹）预处理引起轻微低血压，伴有肾、肠系膜和后肢血管扩张，但 DuP 753 不影响对内皮素 -1 输注的反应。然而，在这些条件下共同输注人α - CGRP（15 nmol·kg⁻¹·h⁻¹）导致内皮素 -1 的肾血管收缩作用持续逆转。
这些结果表明，在没有 DuP 753 的情况下，人α - CGRP 未能使内皮素 -1 的肾血管收缩作用持续逆转是由于肾素 - 血管紧张素系统的激活（可能是低血压的结果）。
在第二个实验中，L - NAME（10 mg·kg⁻¹）引起的肾、肠系膜和后肢血管收缩与内皮素 -1 存在时所见相似。然而，人α - CGRP（15 nmol·kg⁻¹·h⁻¹）完全逆转了 L - NAME 的肾血管收缩作用，尽管后者引起的低血压与内皮素 -1 存在时所见相当。这些结果与在 L - NAME 存在下人α - CGRP 缺乏对肾素 - 血管紧张素系统的功能性激活一致。
通过输注人α - CGRP 完全逆转了 L - NAME 对后肢的血管收缩作用，但后肢血流量和血管传导率未升至基线水平以上。因此，这些结果表明，在存在内皮素 -1 时所见的人α - CGRP 后肢充血性血管扩张作用是由一氧化氮介导的机制所致。
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