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Nitric Oxide Signaling in the Cardiovascular System

Nitric oxide (NO) is produced in the vascular system by endothelial nitric oxide synthase (eNOS), a Ca+2/calmodulin (CaM)-dependent enzyme. NO production is promoted by diverse agonists that transiently increase intracellular Ca+2 concentration and activate eNOS. For example, interaction of eNOS with caveolin, the structural scaffolding protein of caveolae reduces eNOS activity. The calveolin-eNOS complex undergoes cycles of association and dissociation modulated by Ca+2 concentrations. Other regulators of eNOS action include HSP90 and Akt which synergistically increase eNOS activity along with formation of a ternary complex comprised of HSP90, Akt, and CaM-bound eNOS...

Nitric Oxide Signaling in the Cardiovascular System

Pathway Summary

Nitric oxide (NO) is produced in the vascular system by endothelial nitric oxide synthase (eNOS), a Ca+2/calmodulin (CaM)-dependent enzyme. NO production is promoted by diverse agonists that transiently increase intracellular Ca+2 concentration and activate eNOS. For example, interaction of eNOS with caveolin, the structural scaffolding protein of caveolae reduces eNOS activity. The calveolin-eNOS complex undergoes cycles of association and dissociation modulated by Ca+2 concentrations. Other regulators of eNOS action include HSP90 and Akt which synergistically increase eNOS activity along with formation of a ternary complex comprised of HSP90, Akt, and CaM-bound eNOS.In the heart, excitation-contraction (EC) coupling is driven by an ion-channel-mediated calcium cycle that produces myofilament contraction and relaxation. NO in the heart is able to regulate the activaty of ion channels like the L-type Ca(+2). These effects are mediated by cGMP, through the activity of three main proteins: the cGMP-dependent protein kinase (PKG), the cGMP-stimulated phosphodiesterase (PDE2) and the cGMP-inhibited PDE (PDE3). There is also evidence that NO may modulate the function of the ryanodine receptor Ca(2+) release channel (RyR2) on the cardiac sarcoplasmic reticulum.

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