Abstract
During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca(2+) signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.
Highlights
This review will highlight the role played by endogenous nitric oxide (NO) generated in the vascular endothelial cells via endothelial NO-synthase activation and by NO
NO production is regulated by endothelial NO-synthase (eNOS) activation in response to increased cytosolic Ca2+ concentration ([Ca2+]c) in the endothelial cells that binds to calmodulin in order to activate eNOS
The first isoform discovered in the vascular endothelium is present in a large number of cells other than endothelial cells and is the most important isoform participating in vascular relaxation
Summary
This review will highlight the role played by endogenous nitric oxide (NO) generated in the vascular endothelial cells via endothelial NO-synthase (eNOS) activation and by NO released from NO donor compounds in the modulation of the sGC-cGMP-PKG pathway (soluble guanylyl-cyclase, cyclic GMP, protein kinase G) and consequent induction of vasodilatation. It has been shown that calcium ionophore A23187 has the ability to induce [Ca2+]c increase in endothelial cells, with consequent [Ca2+]c decrease in the vascular smooth muscle cells [1] These effects are lower in the aorta of renal hypertensive rats than in the aorta of normotensive rats. A new ruthenium-derived NO donor has been reported to reduce mean arterial pressure in renal hypertensive rats, but not in normotensive rats [3]. This review will summarize data available on the role played by the NO released from endothelial cells and the NO delivered by NO donors in inducing vascular relaxation in conduit and resistance arteries as well as veins
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