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Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

Rodrigues, Gerson J. PhD*; Pereira, Amanda C. PhD; Vercesi, Juliana A. BSc; Lima, Renata G. PhD; Silva, Roberto S. PhD; Bendhack, Lusiane M. PhD

Journal of Cardiovascular Pharmacology: August 2012 - Volume 60 - Issue 2 - p 193–198
doi: 10.1097/FJC.0b013e31825bacc4
Original Article

Abstract: In this study, we investigated the effect of the ruthenium complex [Ru(terpy)(bdq)NO+]3+ (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 Nω-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.

*School of Medicine of Ribeirão Preto

Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.

Reprints: Lusiane M. Bendhack, PhD, Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP. Av. do Café s/n°. 14040-903 Ribeirão Preto, SP, Brazil (e-mail: bendhack@usp.br).

Supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

The authors declare no conflicts of interest.

Received September 27, 2011

Accepted April 22, 2012

© 2012 Lippincott Williams & Wilkins, Inc.