49 research outputs found
Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules.
Carbon monoxide (CO) is a weak soluble guanylyl cyclase stimulator,
leading to transient increases in cGMP and vasodilation. The aim of the present
work was to measure the effect of CO-releasing molecules (CORMs) on the
cGMP/nitric oxide (NO) pathway and to evaluate how selected CORMs affect
NO-induced vasorelaxation.
METHODS AND RESULTS: Incubation of smooth muscle cells with some but not all of
the CORMs caused a minor increase in cGMP levels. Concentration-response curves
were bell-shaped, with higher CORMs concentrations producing lower increases in
cGMP levels. Although exposure of cells to CORM-2 enhanced cGMP formation, we
observed that the compound inhibited NO-stimulated cGMP accumulation in cells and
NO-stimulated soluble guanylyl cyclase activity that could be reversed by
superoxide anion scavengers. Reactive oxygen species generation from CORMs was
confirmed using luminol-induced chemiluminescence and electron spin resonance.
Furthermore, we observed that NO is scavenged by CORM-2. When used alone CORM-2
relaxed vessels through a cGMP-mediated pathway but attenuated NO
donor-stimulated vasorelaxation.
CONCLUSION: We conclude that the CORMs examined have context-dependent effects on
vessel tone, as they can directly dilate blood vessels, but also block NO-induced
vasorelaxation
An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species.
We have designed and synthesised a [Ru(CO)3 Cl2 (NAC)] pro-drug that features an N-acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae [Ru(CO)3 (L)3 ](2+) , including [Ru(CO)3 Cl(glycinate)] (CORM-3), have been shown to produce ROS through a water-gas shift reaction, which contributes significantly, for example, to their antibacterial activity. In contrast, NAC-CORM conjugates do not produce ROS or possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour-necrosis factor (TNF)-α. This work highlights the advantages of combining a CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a unique pro-drug.We thank the EU (Marie Curie CIG to G.J.L.B.), FCT Portugal (FCT Investigator to G.J.L.B.; SFRH/BPD/95253/2013 to J.D.S.) and the EPSRC for funding. The NMR spectrometers are part of The National NMR Facility, supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). G.J.L.B. is a Royal Society University Research Fellow.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/chem.20150247
Efeitos hemorreológicos e cardiovasculares da eritropoietina num modelo de rato em exercÃcio fÃsico sob a acção de drogas
Recombinant human erythropoietin
(rhEPO) has been therapeutically
used for correction of anaemia. However,
due to the increase in circulating
red blood cells (RBCs) it promotes,
thus increasing oxygen delivery to
muscles and improving performance
in sport, it has been also illegally used
as sports doping. Besides the well
known increase of hematocrit and
blood viscosity; which might cause
serious complications for the athletes,
other disturbances could occur, whose
mechanisms remain to be fully elucidated.
This study aimed to evaluate
the hemorheological and cardiovascular
effects of administration of
rhEPO to rats under chronic aerobic
exercise. A ten week-protocol was
performed in four male Wistar rat
groups: control — sedentary; rhEPO
— 50 IV/kg, 3 times/wk; exercised
(EX) — swimming for 1 hr, 3 times/
wk; EX+rhEPO. rhEPO in trained
rats promoted erythrocyte count increase,
hypertension, heart hypertro-phy, sympathetic and serotonergic
overactivation, as well as a trend to
increased oxidative stress. In conclusion,
rhEPO doping in rats under
chronic exercise promotes not only
the expected increased hematocrit,
but also other serious deleterious cardiovascular
and thromboembolic
modifications, including live risk,
which might be known and assumed
by all sports authorities, including
athletes and their physicians.info:eu-repo/semantics/publishedVersio