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

Abstract

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.

Mechanisms underlying the hypotensive and vasodilator effects of Ru(terpy)(bdq)NO]3+, a nitric oxide donor, differ between normotensive and spontaneously hypertensive rats

“…1B). However, in the spontaneously hypertensive rats, the effect of TERPY was not altered by L-NAME infusion, even in a concentration tenfold higher (10 mg/kg) than that used in the previously reported 2-kidney sham-operated and 2-kidney-1-clip study (Rodrigues et al, 2012). These results suggest that the mechanism involved in the modulation of nitric oxide synthase on the hypotensive effect by TERPY would be different in spontaneously hypertensive rats.…”

“…As previously demonstrated, the hypotensive effect of TERPY is higher in 2-kidney-1-clip hypertensive rats and spontaneously hypertensive rats than in their normotensive controls (Rodrigues et al, 2012;Munhoz et al, 2012). Rodrigues et al (2012) demonstrated that L-NAME (1 mg/kg) increased the hypotensive effect of TERPY in 2-kidney sham-operated and 2-kidney-1-clip rats.…”

“…Rodrigues et al (2012) demonstrated that L-NAME (1 mg/kg) increased the hypotensive effect of TERPY in 2-kidney sham-operated and 2-kidney-1-clip rats. In our study, we observed an increased hypotensive effect of TERPY by L-NAME in Wistar rats (Fig.…”

“…The hypotensive effects of new nitric oxide donors were higher in hypertensive as compared with normotensive rats (de Barros et al, 2002;de Gaitani et al, 2009;Rodrigues et al, 2012;Munhoz et al, 2012). However, vasodilation induced by these agents differs in the experimental models of hypertension.…”

Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production

“…[Ru(terpy)(bdq)NO] 3+ (TERPY) is a ruthenium complex NO donor that promotes a hypotensive effect with greater magnitude in hypertensive rats when compared with their normotensive controls [7]; [8]. The TERPY-induced hypotensive effect is slow, long lasting, and it does not lead to reflex tachycardia [7].…”