Effects of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, in L-NAME-induced hypertension in rats

Abstract

PURPOSE:To evaluate the effect of Rut-bpy (Cis-[Ru(bpy) 2 (SO 3 )(NO)]PF 6 ), a novel nitric oxide donor in N -nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut-bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147±16 mmHg compared with 100±19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106±11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained. Keywords: Blood Pressure. Nitric Oxide. Ruthenium. Hypertension. Rats. RESUMO OBJETIVO:Avaliar o efeitos do Rut-bpy (Cis-[Ru (bpy) 2 (SO 3 )(NO)] PF 6 ), um novo doador de óxido nítrico, em ratos hipertensos induzidos pelo éster metílico de N-nitro-L-arginina (L-NAME). MÉTODOS: Vinte e quatro ratos Wistar machos foram distribuídos aleatoriamente em quatro grupos (n = 6), nomeados de acordo com o tratamento aplicado (G1-Salina, G2-Rut-bpy, G3-L-NAME e G4-L-NAME+Rut -bpy). L-NAME (30 mg / Kg) foi injetado por via intraperitoneal 30 minutos antes da administração de Rut-bpy (100 mg / kg). A pressão arterial média (PAM) da aorta abdominal foi monitorada continuamente. RESULTADOS: A pressão arterial média (PAM) em ratos do grupo G3 subiu progressivamente, chegando a 147 ±16 mm Hg, em comparação com 100 ±19 mm Hg em ratos do G1 (p <0,05). Em ratos G4, tratados com L-NAME + Rut-bpy, a PAM atingiu 149±11 milímetros de Hg, enquanto no G2 (ratos tratados com Rut bpy) os valores da PAM foram 106 ±11 mm Hg. No G1 esses valores decresceram progressivamente, atingindo 87±14 mm Hg após 30 minutos. Um achado importante foi a manutenção da PAM durante todo o experimento em ratos do grupo G2. CONCLUSÃO: O uso de Rut bpy não diminui a PAM em ratos hipertensos por L-NAME. No entanto, quando ele é usado em ratos anestesiados, hipotensos, uma pressão arterial estável é obtida. Descritores: Pressão Arterial. Óxido Nítrico. Rutênio. Hipertensão. Ratos.

Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors

“…Many preclinical studies have been performed to support this concept. An NO donor similar to RuBPY, called Rutbpy (Cis-[Ru(bpy) 2 (SO 3 )(NO)]PF 6 ) induced stabilization in BP in anesthetized hypotensive Wistar rats [260]. Cerqueira et al (2008) studied two related nitrosyl-ruthenium complexes, named cis-[Ru(bpy) 2 (SO 3 )(NO)]PF-6-9 (FONO1) and trans-[Ru(NH 3 )4(caffeine)(NO)]C1 3 (LLNO1), which demonstrated a potent vasodilator effect in rabbit corpus cavernosum [261], corroborating the vasodilator potential of these drugs.…”

Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

“…In addition, other NO donors have been developed, which promise advantages over the previous ones, such as spontaneous release of NO under controlled rates. In the literature, we can find descriptions of a variety of these, i.e., donors with higher levels of NO release without being photosensitive or releasing cyanide: for example, Rut-bpy (Cis-[Ru(bpy) 2 (SO 3 )(NO)]PF 6 ) (29) and/or donors with protection against hydrogen peroxide-mediated cytotoxicity diethylamine (DEA/NO) and propylamine propylamine (PAPA/NO) (30). The amount and duration of NO release depend on the pharmacological properties of each donor.…”

Nitric Oxide Donors with Therapeutic Strategic in Experimental <i>Schistossomiasis Mansoni</i>

“…We have previously demonstrated that mice treated with Cis-[Ru(bpy) 2 (NO)SO 3 ](PF 6 ) are more resistant to Paracoccidioidomycosis (PCM) infection, thus, presenting prolonged survival with reduced leukocyte recruitment and TNF-α production in the lung and liver as well as increased production of the anti-inflammatory cytokine IL-10 (Pavanelli et al, 2011). This compound has exhibited interesting biological behavior with promising therapeutical potential such as in brain ischemia/reperfusion (Campelo et al, 2012) and cardiovascular agent (Campelo et al, 2011). Recently, it was showed this ruthenium-based NO-donor can efficiently release nitric oxide upon reaction with thiols, such as glutathione (Silva et al, 2011).…”