Long-lasting hypotensive effect in renal hypertensive rats induced by nitric oxide released from a ruthenium complex.
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.
School of Medicine of Ribeirão Preto †Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
Gerson J
GJ
Rodrigues
Amanda C
AC
Pereira
Juliana A
JA
Vercesi
Renata G
RG
Lima
Roberto S
RS
Silva
Lusiane M
LM
Bendhack
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017975:Ruthenium Compounds / Q000378:metabolism / Q000494:pharmacology*; D013113:Spin Labels; D013997:Time Factors
D000959:Antihypertensive Agents; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D017975:Ruthenium Compounds; D013113:Spin Labels; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester