Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation

Santhanam, Anantha Vijay R.; Viswanathan, Shiv Kumar; Dikshit, Madhu

doi:10.1016/j.ejphar.2007.06.031

Cited by 41 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that agmatine has an important role in regulating the production of NO by inhibiting neuronal and inducible NOS and stimulating endothelial NOS (Satriano, 2003;Halaris and Plietz, 2007;Santhanam et al, 2007). Interestingly, there were parallel changes in agmatine and total NOS activity in the CA2/3 PRC, POR and TE, however with the reversed patterns in the CA1 and PFC.…”

Section: Age-related Changes In Arginine Metabolismmentioning

confidence: 84%

Ageing alters behavioural function and brain arginine metabolism in male Sprague–Dawley rats

Gupta

Collie

et al. 2012

Neuroscience

View full text Add to dashboard Cite

Section: Age-related Changes In Arginine Metabolismmentioning

confidence: 84%

Ageing alters behavioural function and brain arginine metabolism in male Sprague–Dawley rats

Gupta

Collie

et al. 2012

Neuroscience

View full text Add to dashboard Cite

“…The observation that RX821002 did not completely attenuate agmatine-triggered relaxation implied that agmatine affecting relaxation partly via α-AR independent pathway. Recently, agmatine’s relaxing effects in rat aorta are documented to be via small conductance Ca 2+ -activated K + channel and ATP-sensitive inward rectifying K + channels, and idazoxan failed to inhibit these relaxations [52]. It appears that rat aorta is devoid of I-receptors, as Musgrave et al [53] have reported the absence of I-receptor antagonist effects, and thus it is likely that agmatine is using alternative pathways of aortic relaxation.…”

Section: Discussionmentioning

confidence: 99%

Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension

et al. 2013

View full text Add to dashboard Cite

L-arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. L-arginine initiated relaxations (EC50, 5.8 ± 0.7 mM; n = 9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3 ± 1.3 mM; n = 5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7 ± 12.1 μM; n = 22), which was compromised by L-NAME (L-NG-Nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9 ± 23.4 μM; n = 5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension.

show abstract

“…The presence of a functional endothelium was then assessed by measuring relaxation to ACh (3 nM to 30 mM) in PE (1 μM) precontracted rings. Finally, tissue contractility and viability were assessed by exposing the rings to KCl Krebs buffer (80 mM) in all the groups [30].…”

Section: Vascular Reactivitymentioning

confidence: 99%

A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters

et al. 2011

Self Cite

View full text Add to dashboard Cite

The present study was undertaken to assess the chronology of major pathological events associated with high cholesterol (HC) diet and their modulation by anti-platelet drugs. Male Golden Syrian hamsters were fed HC diet up to 90 days. Plasma lipid, glucose and coagulation parameters (commercial kits), platelet activation (whole blood aggregation and static adhesion), endothelial dysfunction (aortic ring vasoreactivity), splenocyte TNF-α, IFN-γ and iNOS mRNA transcripts (RT-PCR), and ferric chloride (time to occlusion) induced thrombosis were monitored at 15, 30, 60, and 90 days after HC feeding and compared with normolipidemic hamsters. A significant increase in plasma lipid levels was observed at 15 days of HC feeding, but other parameters remain unaltered. Enhanced ADP, collagen, and thrombin-induced platelet aggregation, splenocyte TNF-α expression along with endothelial dysfunction were observed from 30 to 90 days of HC feeding. Platelet adhesion on collagen-/fibrinogen-coated surface and IFN-γ expression were augmented only after 60 days, while enhanced iNOS expression, reduction in thrombin time, and potentiation of ferric chloride-induced thrombosis was observed only at 90 days of HC feeding. Thus, pathological changes induced by HC diet depend on the duration and extent of hyperlipidemia. Moreover, hamsters treated with anti-platelet drugs aspirin (5 mg/kg) or clopidogrel (10 mg/kg) along with HC feeding exhibited reduction in platelet activation as well as subsequent changes observed in the abovementioned parameters following HC feeding. Since reduction in TNF-α was associated with reversion in endothelial dysfunction and prothrombotic state, the role of platelets is implicated in the pathological changes associated with HC feeding.

show abstract

Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation

Cited by 41 publications

References 46 publications

Ageing alters behavioural function and brain arginine metabolism in male Sprague–Dawley rats

Ageing alters behavioural function and brain arginine metabolism in male Sprague–Dawley rats

Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension

A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters

Contact Info

Product

Resources

About