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 (… Show more
“…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.…”
Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.
“…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.…”
Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.
“…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.…”
Physiological evidence indicates that the supraoptic nucleus (SON) is an
important region for integrating information related to homeostasis of body
fluids. Located bilaterally to the optic chiasm, this nucleus is composed of
magnocellular neurosecretory cells (MNCs) responsible for the synthesis and
release of vasopressin and oxytocin to the neurohypophysis. At the cellular
level, the control of vasopressin and oxytocin release is directly linked to the
firing frequency of MNCs. In general, we can say that the excitability of these
cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane
properties of the MNCs themselves and 2) synaptic input from circumventricular
organs that contain osmosensitive neurons. It has also been demonstrated that
MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the
study of their intrinsic membrane properties became imperative to explain the
osmosensitivity of MNCs. In addition to this, the discovery that several
neurotransmitters and neuropeptides can modulate their electrical activity
greatly increased our knowledge about the role played by the MNCs in fluid
homeostasis. In particular, nitric oxide (NO) may be an important player in
fluid balance homeostasis, because it has been demonstrated that the enzyme
responsible for its production has an increased activity following a hypertonic
stimulation of the system. At the cellular level, NO has been shown to change
the electrical excitability of MNCs. Therefore, in this review, we focus on some
important points concerning nitrergic modulation of the neuroendocrine system,
particularly the effects of NO on the SON.
“…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).…”
Schistosomiasis, an immune disease, remains a major public health problem in endemic area. To determine the influence of Nitric Oxide (NO) on this disease, we tested two compounds (Trans-[Ru(bpy) 2 (NO)SO3](PF)-PF 6 and Na 2 [Fe(CN) 5 (NO)]-SNP, which releases NO when activated by biological reducing agents, in BALB/c mice infected subcutaneously by Schistosoma BH strains. The parasitic activity of NO-donors was evaluated in this model by measuring the immune cellular response in liver with: Cytokines levels; histopathological characteristics and the number of the granulomatous lesions; and NO levels. We found that NO-donors treated mice were more resistant to infection, since they exhibited higher survival. Furthermore, we observed in histopathological analysis a decreased influx of inflammatory cells in the hepatic tissue of mice treated with both donors. The parasite counting (estimated as eggs and worms number) was also minor in treated mice. Moreover, decreased levels of IL-10 were detected in the liver of infected mice treated with SNP. The animals treated with PF 6 showed high plasmatic NO levels at 45 days after infection. Altogether, these data suggest that NO is a pivotal factor of resistance during schistossomiasis by controlling parasites proliferation, influencing cytokine production and consequently modulating the development of inflammatory response.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.