左旋硝基精氨酸所致肺动脉高压大鼠外周血管多巴胺-1受体反应性的变化

Changes in Responsiveness of Dopamine Receptors in Some Peripheral Vessels in L NNA Induced Pulmonary Artery Hypertension in Rats

为研究一氧化氮合酶抑制剂左旋硝基精氨酸诱导的肺动脉高压大鼠各部位离体血管环对多巴胺－ １ 受体反应性的影响，采用大鼠肺动脉、肠系膜动脉和肾动脉离体血管标本，在去甲肾上腺素收缩血管后，用多巴胺－ １ 受体选择性激动剂非诺多泮使血管舒张，所有实验在吲哚美辛（１０ μｍｏｌＬ） 和普萘洛尔（３ μｍｏｌＬ） 存在下进行。左旋硝基精氨酸组大鼠各动脉对非诺多泮的反应性均有不同程度的降低，以肺动脉最明显，最大舒张占预收缩的百分比为４５．５％ ±４．１％ ，低于对照组的９７．３ ％ ±１０ ．６ ％（ Ｐ＜ ０．０１）；亲合常数为２０４２ ±２２１，低于对照组的４２７４ ．２±５１２（Ｐ＜ ０．０１） ，接近对照组的去内皮水平。肠系膜动脉和肾动脉对非诺多泮的反应性亦有下降，但下降程度明显低于肺动脉。结果提示，内皮依赖性受体介导多巴胺－ １ 的舒张效应降低是左旋硝基精氨酸形成肺动脉高压的因素之一。

Aim The vasorelaxation responses of some peripheral vessels to fenoldopam, a selective dopamine-1 receptor agonist, were observed in N G-nitro-L-arginine (L-NNA), a selective NO synthase antagonist, induced pulmonary artery hypertension (PAH) rats. Methods Rings of rat pulmonary, renal, mesenteric artery were to dopamine-1 (DA 1) receptor agonist responsiveness. All experiments were performed in the presence of indomethacin (10 μmol/L) and propranolol (3 μmol/L) to prevent the production of vasoactive prostanoids and the binding of norepinephrinewith beta receptor. Results It was shown that, during the development of PAH, the vasorelaxation responses to fenoldopam were significantly reduced in peripheral vessels, especially in the pulmonary vessel. After 28days, the Emax (%) in the pulmonary artery was 45.5%±4.1%, being lower than the control group of 97.3%±10.6% and the K A was 2042±221, being lower than the control group of 4272±512 (P<0.01), while in the mesenteric and renal vessels, the vasorelaxation responses were only moderately decreased after 28 days. Conclusion There results show that the detereorated peripheral vessels DA 1 receptor-mediated vasorelaxation might be one of the mechanisms underlying development of hypertension.