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

Anantha Vijay R. Santhanam, Shivkumar Viswanathan, Madhu Dikshit

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The ability of agmatine, formed from l-arginine by the enzyme arginine decarboxylase (ADC), to modulate vasomotor function in rat aorta was investigated in the present study. Agmatine-mediated modulation of vasomotor tone was studied in organ chambers, protein expression quantified by Western blot analysis and cyclic guanosine 5′-monophosphate (cGMP) levels measured by radioimmunoassay. Agmatine (10- 10 to 10- 3 M) produced concentration-dependent relaxations (82 ± 5%) in phenylephrine-contracted endothelium intact rat aorta. Relaxations to agmatine were diminished on denudation of endothelium and nitric oxide synthase (NOS) inhibition by l-Nω-nitro arginine or soluble guanylate cyclase inhibition by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (P < 0.001) abolished agmatine-mediated relaxations, while relaxations were insensitive to inducible NOS inhibition by 1400W. Agmatine-treated aorta demonstrated increased protein expression of phosphorylated S473-Akt and phosphorylated S1177-endothelial nitric oxide synthase (eNOS), and elevated the levels of cyclic GMP (P < 0.01). Agmatine-mediated potentiation of relaxations and elevation of cGMP levels was sensitive to phosphatidylinositol 3′-kinase inhibitor, wortmannin. Relaxations to agmatine were also affected by pre-treatment with tetraethylammonium (P < 0.01) or apamin (P < 0.05), and were not affected by charybdotoxin. Relaxations to agmatine were partially affected by pre-treatment of aortic rings with barium chloride (P < 0.05), and glybenclamide (P < 0.05). Results obtained suggest that agmatine activates protein kinase B/Akt to phosphorylate eNOS and elevate cyclic GMP levels to produce vasodilatation of aorta. Agmatine-mediated relaxations in rat aorta seems to be mediated mainly by endothelial NO-mediated activation of small conductance Ca2+-activated K+ channels, and partly by ATP-sensitive and inward rectifying K+ channels.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Oct 31 2007


  • Akt
  • Nitric oxide synthase
  • Potassium channels
  • Rat aorta
  • Soluble guanylate cyclase
  • Vasorelaxation

ASJC Scopus subject areas

  • Pharmacology


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