_Dr. Eiserich_eiserich-2

_Dr. Eiserich_eiserich-2 - Nitric Oxide: Part 2 Role in...

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Nitric Oxide: Part 2 Role in Vascular Physiology and Disease Jason P. Eiserich Department of Internal Medicine School of Medicine University of California, Davis Email: jpeiserich@ucdavis.edu Tel: (530) 752-4010
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Biosynthesis of nitric oxide
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NO-Mediated Vasodilation
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Shear GC i eNOS NO eNOS NO NO NO Agonist GC a cGMP Nitric Oxide-Dependent Signaling in the Vasculature
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1998 Nobel Prize in Medicine “...discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system”
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Murad’s Mechanism of Action for nitrovasodilators ONO 2 ONO 2 ONO 2 O O O 2 NO ONO 2 ONO Nitroglycerin Isosorbide dinitrate Amyl nitrite RONO 2 RONO 2 RONO glutathione-S-transferase Flavoprotein (FMN) NAD(P)H NAD(P) + GSH GSNO NO • Used in the treatment of angina (Even Alfred Nobel himself) • Administered sublingually or transdermal • Decreases arterial pressure
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Furchgott’s “Sandwich”
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Ignarro’s Spectral Analysis
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Heme Proteins and Metals as Targets of NO Soluble Guanylate Cyclase Participates in catalysis Fe II Fe II NO porphyrin ring porphyrin ring Histidine ligand N NH R N NH R NO inactive guanylate cyclase activated guanylate cyclase Guess what? Many forms of metals are radicals!
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Role of S-Nitrosothiols in Blood Scharfstein J.S. et al J. of Clin . Invest. (1994) 94(4): 1432-1439 ; Jie et al Nature (1996) 280:221-226 Circulating NO “pool” as S-nitroso albumin which can
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_Dr. Eiserich_eiserich-2 - Nitric Oxide: Part 2 Role in...

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