Henrion D, Dowell F J, Levy B I, Michel J B
Institut National de la Santé et de la Recherche Médicale (INSERM) U141, IFR Circulation-Lariboisière, Université Paris VII, Hôpital Lariboisière, France.
Hypertension. 1996 Sep;28(3):361-6. doi: 10.1161/01.hyp.28.3.361.
Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K+ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, K+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 +/- 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 +/- 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 +/- 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats.
长期给予NG-硝基-L-精氨酸甲酯（L-NAME）可导致血压升高，而血管紧张素I转换酶抑制剂或血管紧张素II受体（1型）阻滞剂可预防这种升高。该模型中血管反应性的改变尚未得到广泛研究，可能与L-NAME诱导的高血压发病机制有关。在本研究中，我们旨在研究从用L-NAME或L-NAME加转换酶抑制剂喹那普利治疗3周的Wistar大鼠分离的主动脉环段的血管反应性和cGMP含量。喹那普利可预防L-NAME治疗大鼠的血压升高，尽管在L-NAME和L-NAME加喹那普利治疗的大鼠中，乙酰胆碱诱导的主动脉环舒张均受到抑制，而硝普钠诱导的舒张增加。在分离的主动脉环段中，长期给予L-NAME可降低对K+（125 mmol/L）、去氧肾上腺素、血管紧张素II、G蛋白刺激剂AlF4-和蛋白激酶C激活剂佛波酯二丁酸酯的收缩反应。与上调的硝普钠诱导的舒张相反，喹那普利可恢复主动脉对血管紧张素II、去氧肾上腺素、AlF4-、K+和佛波酯二丁酸酯的收缩能力。与对照组（1798±522 fmol/mg蛋白，n = 12）相比，L-NAME治疗组（530±120 fmol/mg蛋白，n = 12，P <.05）和L-NAME加喹那普利治疗组（461±140 fmol/mg蛋白，n = 12，P <.05）的主动脉cGMP降低。我们假设L-NAME持续阻断一氧化氮可能会减弱持续的内源性舒张张力，并与大动脉中上调的内源性血管收缩张力有关。在L-NAME治疗大鼠的大动脉壁中，转换酶抑制对增加的内源性收缩张力的干扰比对降低的血管舒张张力的干扰更大。
