Nitric Oxide (NO) in Vascular Biology

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Synthesis:
    • Precursor:
      • L-arginine
    • Enzyme: 
      • Nitric oxide synthase (NOS):
        • Converts L-arginine → NO + citrulline
    • Cofactors: 
      • Oxygen, NADPH, tetrahydrobiopterin (BH4), FAD, FMN
    • NOS Isoforms:
      • eNOS (endothelial NOS):
        • Maintains vascular tone
        • Anti-thrombotic
      • nNOS (neuronal NOS):
        • Neurotransmission
        • Smooth muscle relaxation in GI tract
        • Penile erection
      • iNOS (inducible NOS):
        • Macrophages during inflammation:
          • Produces large amounts of NO:
            • For microbicidal and cytotoxic activity
  • Mechanism of Action:
    • NO diffuses into adjacent vascular smooth muscle cells
    • Activates soluble guanylate cyclase (sGC):
      • Increasing cGMP:
        • cGMP activates protein kinase G (PKG):
          • Decreases intracellular Ca²⁺:
            • Vascular smooth muscle relaxation (vasodilation)
    • This process is rapid, short-lived:
      • Due to NO’s gaseous and diffusible nature
  • Physiologic Roles:
    • Vasodilation: 
      • Maintains baseline vascular tone
      • Prevents hypertension
    • Anti-thrombotic: 
      • Inhibits platelet aggregation and adhesion to endothelium
    • Anti-inflammatory: 
      • Inhibits leukocyte adhesion to endothelium
    • Endothelial protection: 
      • Limits smooth muscle proliferation (anti-atherogenic)
    • Neurotransmission: 
      • nNOS-derived NO acts as a neurotransmitter:
        • Penile erection
        • GI peristalsis
    • Host defense:
      • iNOS in macrophages generates high NO levels:
        • Bactericidal and tumoricidal effects
    • Endothelium-Derived Relaxing Factor (EDRF):
      • NO was historically discovered as EDRF:
        • The key mediator of endothelium-dependent vasodilation:
          • Demonstrated that the endothelium is not passive but actively regulates vascular tone
    • Counter-Regulation: Endothelin:
      • Endothelin-1 (ET-1): 
        • Potent vasoconstrictor peptide secreted by endothelial cells:
          • Acts through ETA and ETB receptors on vascular smooth muscle:
            • ↑ Ca²⁺ influx → vasoconstriction
          • Provides balance against NO-mediated vasodilation, maintaining vascular homeostasis
  • Clinical Relevance:
    • Hypertension, atherosclerosis, diabetes: 
      • Impaired endothelial NO production → endothelial dysfunction → vasoconstriction, thrombosis risk
    • Pharmacology:
      • Nitroglycerin, isosorbide dinitrate: 
        • Prodrugs → release NO → vasodilation (angina, heart failure)
      • Sildenafil (Viagra): 
        • Inhibits phosphodiesterase-5 (PDE-5) → prevents cGMP breakdown → potentiates NO-mediated vasodilation → erectile dysfunction therapy, pulmonary hypertension
    • Sepsis: 
      • Excessive NO from iNOS → systemic vasodilation → hypotension / shock
    • Asthma/COPD: 
      • Exhaled NO is a biomarker of airway inflammation
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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