RESUMEN
Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91phox expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Asunto(s)
Angiotensina I/antagonistas & inhibidores , Hipertensión/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Fragmentos de Péptidos/antagonistas & inhibidores , Cloruro de Sodio Dietético/farmacología , Angiotensina I/metabolismo , Animales , Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/inducido químicamente , Masculino , Fragmentos de Péptidos/metabolismo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.
Asunto(s)
Hipertensión/tratamiento farmacológico , Metformina/farmacología , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Cloruro de Sodio Dietético/farmacología , Animales , Antioxidantes/uso terapéutico , Presión Arterial/efectos de los fármacos , Hipertensión/inducido químicamente , Infusiones Intraventriculares , Masculino , Metformina/administración & dosificación , Neurotransmisores/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Objective To explore the advantages of MR imaging sequences displaying the epidermoid cyst (EC) with adjacent neurovascular invasion in the cerebellopontine angle region.Methods Petrospective analysis on clinical and MR imaging data of 8 patients with ECs in the cerebellopontine angle region confirmed by surgery and pathology was performed. T1WI, T2WI, FLAIR,DWI, T1 enhancement scanning, and both 3D-FIESTA and 3D-TOF-MRA sequences, especially, were performed to investigate the normal neurovascular signal features, epidermoid cyst and its neurovascular invasion features in cerebellopontine angle region and the advantages of 3D-FIESTA and 3D-TOF-MRA sequences in demonsuating these features were analyzed too. Results Conventional sequences showed poor results on nerves and vessels, but 3D-FIESTA showed clear results. Vessels were clearly showed under 3D-TOF-MRA, but nerves shown under 3D-TOF-MRA were not as clear as those under 3D-FIESTA. Eight ECs showed isointensity in 3D-FIESTA, and the border of the lesions could be delineated clearly from peripheral CSF. However, hypointensity was showed in 3D-TOF-MRA, and the borders of the lesions could not be identified from CSF. All of the 8 patients with ECs (100%) showed trigeminal nerve encasement on 3D-FIESTA, including 4 thinning and 2 fold distortion. In the 8 patients with ECs, 3 (37.5%) showed facial and acoustic nerves encasement (1 was also diagnosed as having dysaudia by clinical manifestations), 1 (12.5%) displacement, 2 (25%) tight relationship, and 2 (25%)non-touching. Clinically, all 8 patients with ECs had trigeminal neuralgia; of them, the 2nd and 3ndtrigeminal nerves were involved in 4 patients and the 1at, 2nd and 3nd trigeminal nerves were all involved in the other 4 patients; the imaging features and clinical manifestations were 100% coincident. Conclusion 3D-FIESTA sequence is superior to other MR imaging sequences in demonstrating the ECs with neurovascular invasion; combined with 3D-TOF MRA, 3D-FIESTA can give precise preoperative evaluation.