Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta

Ford, Rebecca J.; Graham, Drew A.; Denniss, Steven G; Quadrilatero, Joe; Rush, James W. E.

doi:10.1016/j.freeradbiomed.2005.09.020

Cited by 25 publications

(32 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is believed that this selective increase in GSH in glial cells is a protective mechanism to increase neuronal survival upon oxidative stress [40]. This cell selectivity could also be displayed by blood vessels as it has recently been reported that BSO was able to blunt endotheliumdependent relaxation of aortic preparations, despite the increase in vascular smooth muscle contractility [41]. Moreover, our results clearly point to an involvement of mitochondrial GSH in functional GSNO generation.…”

Section: Discussionsupporting

confidence: 75%

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

Triguero

González-Herreros

Costa

et al. 2007

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Using a nitric oxide (NO)-specific fluorescent probe, we have examined the location of NO generation in the urethra from sheep and rat when induced by either electrical field- or light-stimulation (EFS and LS, respectively). In addition, we studied the effect of specific glutathione (GSH) modifiers, acting upon different cellular GSH pools, on NO release and on urethral relaxation. Both EFS and LS led to fluorescence emission from a fiber network associated with neuronal NO synthase (nNOS) immunoreactive nerves. Both the relaxation and the fluorescence elicited by EFS were blocked by specific nNOS inhibitors, but these parameters were not significantly modified by endogenous GSH depletion. In contrast, the opposite was found for LS-induced responses. Moreover, when the mitochondrial pool was effectively reduced by incubation with ethacrynic acid, the responses to LS were further reduced until they disappeared after intensive LS. Our results confirm that while NO is released by nNOS activation, the photolytic breakdown of an endogenous nitro-compound, probably S-nitroso-glutathione, in nitrergic nerves (and in the vascular endothelium) is the only factor responsible for photo-relaxation. The possible role of this mechanism in NO inactivation and as a protective mechanism in NO-generating structures is further discussed.

show abstract

Section: Discussionsupporting

confidence: 75%

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

Triguero

González-Herreros

Costa

et al. 2007

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…In BSO-treated rats as well, reduced adiponectin mRNA levels are observed, suggesting that oxidative stress induced by BSO affects adipose tissue. Glutathione depletion following BSO administration has been reported to increase tissue H 2 O 2 levels in vivo (Ford et al, 2006). We and others have shown that H 2 O 2 decreases the production of adiponectin in adipocytes Kamigaki et al, 2006), which presumably reduces adiponectin production in adipose tissue, resulting in hypoadiponectinemia in BSO-treated rats.…”

Section: Discussionmentioning

confidence: 70%

Buthionine sulfoximine causes endothelium dependent hyper-relaxation and hypoadiponectinemia

Iwata¹,

Wang²,

Uchida³

et al. 2007

Life Sciences

View full text Add to dashboard Cite

“…The thoracic aorta was excised and 2-mm aortic rings were prepared for vascular myography as previously described (21). In some experiments, the endothelium was removed by inserting a 256 m diameter titanium wire through the vessel lumen and rolling it on Whatman blotting paper (Whatman, Maidstone, England) soaked with 4°C Krebs-bicarbonate buffer.…”

Section: Vasomotor Responses In Isolated Vesselsmentioning

confidence: 99%

“…Consistent removal of the endothelium by this method was verified functionally by nonresponsiveness to a maximal dose of the endothelium-dependent vasodilatory agent ACh in phenylephrine (PE) preconstricted aortic rings and biochemically by substantial removal of eNOS protein content (i.e., Ͻ10 -15% residual eNOS compared with endothelium-intact aortic rings from the same animals) assessed by Western blotting (data not shown). Rings were mounted onto a vascular myography apparatus (Radnotti, Monrovia, CA) where they were immersed in 37°C Krebs-bicarbonate buffer continuously aerated with 95% O 2-5% CO2, and data were collected as already described (21). Gradual stretching to a predetermined optimal resting tension of 7 g (24) was achieved by increasing the tension by 0.5 g increments from 1 g every 5 min, and rings were equilibrated at optimal resting tension for 30 min.…”

Section: Vasomotor Responses In Isolated Vesselsmentioning

confidence: 99%

“…The time from removal of the rings from the buffer to immersion in liquid nitrogen was Ͻ5 s. One ring was removed for each control point and AICAR dose, and all rings (controls and AICAR doses) were obtained from a single rat for each E ϩ or E Ϫ experiment. Sample preparation and immunoblotting procedures were performed as described previously (21). Briefly, 30 g of protein were loaded per well, and membranes were Ponceau stained to confirm consistent protein loading across lanes.…”

Section: Immunoblot Analysis Of Protein Content and Phosphorylation Lmentioning

confidence: 99%

See 1 more Smart Citation

Endothelium-dependent vasorelaxation to the AMPK activator AICAR is enhanced in aorta from hypertensive rats and is NO and EDCF dependent

Ford

Rush

2011

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Ford RJ, Rush JW. Endothelium-dependent vasorelaxation to the AMPK activator AICAR is enhanced in aorta from hypertensive rats and is NO and EDCF dependent. Am J Physiol Heart Circ Physiol 300: H64 -H75, 2011. First published October 22, 2010 doi:10.1152/ajpheart.00597.2010.-Activation of AMP-activated protein kinase (AMPK) induces vasorelaxation in arteries from healthy animals, but the mechanisms coordinating this effect are unclear and the integrity of this response has not been investigated in dysfunctional arteries of hypertensive animals. Here we investigate the mechanisms of relaxation to the AMPK activator 5-aminoimidazole-4-carboxamide 1-␤-D-ribofuranoside (AICAR) in isolated thoracic aorta rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Although AICAR generated dose-dependent (10 Ϫ6 -10 Ϫ2 M) relaxation in precontracted WKY and SHR aortic rings with (E ϩ ) or without (E Ϫ ) endothelium, relaxation was enhanced in E ϩ rings. Relaxation in SHR E ϩ rings was also enhanced at low [AICAR] (10 Ϫ6 M) compared with that of WKY (57 Ϯ 8% vs. 3 Ϯ 2% relaxation in SHR vs. WKY E ϩ ), but was similar and near 100% in both groups at high [AICAR]. Pharmacological dissection showed that the mechanisms responsible for the endothelium-dependent component of relaxation across the dose range of AICAR are exclusively nitric oxide (NO) mediated in WKY rings, but partly NO dependent and partly cyclooxygenase (COX) dependent in SHR vessels. Further investigation revealed that AChstimulated COX-endothelium-derived contracting factors (EDCF)-mediated contractions were suppressed by AICAR, and this effect was reversed in the presence of the AMPK inhibitor Compound C in quiescent E ϩ SHR aortic rings. Western blots demonstrated that P(Thr 172 )-AMPK and P(Ser 79 )-acetyl-CoA carboxylase (indexes of AMPK activation) were elevated in SHR versus WKY E ϩ rings at low AICAR (ϳ2-fold). Together these findings suggest that AMPKmediated inhibition of EDCF-dependent contraction and elevated AMPK activation may contribute to the enhanced sensitivity of SHR E ϩ rings to AICAR. These results demonstrate AMPK-mediated vasorelaxation is present and enhanced in arteries of SHR and suggest that activation of AMPK may be a potential strategy to improve vasomotor dysfunction by suppressing enhanced endoperoxidemediated contraction and enhancing NO-mediated relaxation.spontaneously hypertensive rats; Wistar-Kyoto rats; nitric oxide; adenosine 5=-monophosphate-activated protein kinase; 5-aminoimidazole-4-carboxamide 1-␤-D-ribofuranoside; endothelium-derived contracting factors AMP-ACTIVATED PROTEIN KINASE (AMPK) is emerging as a potential regulator of vascular function. Although recognized primarily as a modulator of cellular energy status and metabolism (28, 57), the identification of its existence in vascular cells and of its ability to be stimulated by numerous physical (8,20,59), energetic (17), hormonal (5, 8, 43), and chemical (8, 9, 11, 12, 29, 35, 40, 53) mediators of vasomotor function suggest a p...

show abstract

Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta

Cited by 25 publications

References 32 publications

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

Buthionine sulfoximine causes endothelium dependent hyper-relaxation and hypoadiponectinemia

Endothelium-dependent vasorelaxation to the AMPK activator AICAR is enhanced in aorta from hypertensive rats and is NO and EDCF dependent

Contact Info

Product

Resources

About