School of Medicine of Ribeirão Preto †Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
J Cardiovasc Pharmacol. 2012 Aug;60(2):193-8. doi: 10.1097/FJC.0b013e31825bacc4.
In this study, we investigated the effect of the ruthenium complex [Ru(terpy)(bdq)NO] (TERPY) on the arterial pressure from renal hypertensive 2 kidney-1 clip (2K-1C) rats, which was compared with sodium nitroprusside (SNP). The most interesting finding was that the intravenous bolus injection of TERPY (2.5, 5.0, 7 mg/kg) had a dose-dependent hypotensive effect only in 2K-1C rats. On the other hand, SNP (35 and 70 μg/kg) presented a similar hypotensive effect in both normotensive (2K) and 2K-1C although the effect of 70 μg/kg was >35 μg/kg. The injection of the nonselective NO-synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) increased the arterial pressure in 2K and 2K-1C rats with a similar magnitude. After infusion of L-NAME, the hypotensive effect induced by TERPY and SNP was potentiated in both 2K and in 2K-1C rats. The administration of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl increased the hypotensive effect induced by TERPY or SNP in both 2K and 2K-1C rats. The hypotensive effect induced by TERPY was longer than that produced by SNP. Taken together, our results show that the TERPY has a long-lasting hypotensive effect, which has a dose dependence and higher magnitude in 2K-1C compared with in 2K rats. In comparison with SNP, TERPY is less potent in inducing arterial pressure fall, but it presents a much longer hypotensive effect.
在这项研究中，我们研究了钌配合物[Ru(terpy)(bdq)NO]（TERPY）对肾性高血压 2 肾 1 夹（2K-1C）大鼠动脉压的影响，并将其与硝普钠（SNP）进行了比较。最有趣的发现是，TERPY（2.5、5.0、7 mg/kg）静脉推注仅在 2K-1C 大鼠中具有剂量依赖性降压作用。另一方面，SNP（35 和 70 μg/kg）在正常血压（2K）和 2K-1C 大鼠中均呈现出相似的降压作用，尽管 70 μg/kg 的作用大于 35 μg/kg。非选择性一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯（L-NAME）的注射使 2K 和 2K-1C 大鼠的动脉压升高，幅度相似。在 L-NAME 输注后，TERPY 和 SNP 诱导的降压作用在 2K 和 2K-1C 大鼠中均增强。超氧化物清除剂 4-羟基-2,2,6,6-四甲基哌啶-N-氧自由基的给药增加了 TERPY 或 SNP 在 2K 和 2K-1C 大鼠中诱导的降压作用。TERPY 诱导的降压作用比 SNP 诱导的降压作用持续时间更长。综上所述，我们的结果表明，TERPY 具有持久的降压作用，在 2K-1C 大鼠中比在 2K 大鼠中具有更强的剂量依赖性和更大的降压作用。与 SNP 相比，TERPY 诱导动脉压下降的作用较弱，但它具有更长的降压作用。
