1.Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes.
Xu Z1, Park SS, Mueller RA, Bagnell RC, Patterson C, Boysen PG. Cardiovasc Res. 2005 Mar 1;65(4):803-12.
OBJECTIVE: To examine if adenosine prevents oxidant-induced mitochondrial dysfunction by producing nitric oxide (NO) in cardiomyocytes.
2.Monitoring of in vivo manipulation of nitric oxide synthases at the rat retina using the push-pull perfusion sampling and capillary electrophoresis.
Pritchett JS1, Shippy SA2. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Apr 1;955-956:81-5. doi: 10.1016/j.jchromb.2014.02.022. Epub 2014 Feb 22.
Proteins play a variety of functional roles in tissues that underlie tissue health. The measurement of protein function is important to both understand normal and dysfunctional tissue states. Low-flow push-pull perfusion sampling (LFPS) has been used to collect submicroliter volumes of extracellular fluid which are well suited to capillary electrophoresis for compositional quantitative analysis. In this study, LFPS is used to deliver pharmacological agents to the in vivo retinal tissues at the probe sampling tip during sampling to measure protein function. Two native nitric oxide synthase enzymes were pharmacologically inhibited and the enzyme product NO metabolite, nitrate, was determined with capillary electrophoresis from the perfusates. LFPS delivered inhibitors including the non-selective N(G)-nitro-Larginine methyl ester (L-NAME), the nNOS selective 7-nitroindazole (7-NI), and eNOS N5-(1-imioethyl)-L-ornithine, dihydrochloride (L-NIO) were perfused to the sampling region either directly over a rat retina optic nerve head or 1-mm peripheral to the ONH.
3.Intermedin in paraventricular nucleus attenuates sympathetic activity and blood pressure via nitric oxide in hypertensive rats.
Zhou YB1, Sun HJ, Chen D, Liu TY, Han Y, Wang JJ, Tang CS, Kang YM, Zhu GQ. Hypertension. 2014 Feb;63(2):330-7. doi: 10.1161/HYPERTENSIONAHA.113.01681. Epub 2013 Nov 11.
Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N(ω)-propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride.
4.Phosphodiesterase 5 inhibitors prevent 3,4-methylenedioxymethamphetamine-induced 5-HT deficits in the rat.
Puerta E1, Hervias I, Goñi-Allo B, Lasheras B, Jordan J, Aguirre N. J Neurochem. 2009 Feb;108(3):755-66. doi: 10.1111/j.1471-4159.2008.05825.x.
Phosphodiesterase 5 (PDE5) inhibitors are often used in combination with club drugs such as 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). We investigated the consequences of such combination in the serotonergic system of the rat. Oral administration of sildenafil citrate (1.5 or 8 mg/kg) increased brain cGMP levels and protected in a dose-dependent manner against 5-hydroxytryptamine depletions caused by MDMA (3 x 5 mg/kg, i.p., every 2 h) in the striatum, frontal cortex and hippocampus without altering the acute hyperthermic response to MDMA. Intrastriatal administration of the protein kinase G (PKG) inhibitor, KT5823 [(9S, 10R, 12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid, methyl ester)], suppressed sildenafil-mediated protection. By contrast, the cell permeable cGMP analogue, 8-bromoguanosine cyclic 3',5'-monophosphate, mimicked sildenafil effects further suggesting the involvement of the PKG pathway in mediating sildenafil protection.