eNOS
Optimization
Targeting transcriptional upregulation, post-translational modifications, and cofactor stabilization for maximum enzymatic efficiency.
Transcriptional Upregulation
Increasing the absolute quantity of eNOS enzyme by stimulating the NOS3 gene promoter.
Shear Stress & Flow
Laminar shear stress activates mechanoreceptors that trigger KLF2 and KLF4 transcription factors, binding to the NOS3 promoter .
Laminar Flow
Steady, aerobic exercise (Zone 2) → ↑ eNOS mRNA
Turbulent Flow
Hypertension / Plaque → ↓ eNOS mRNA
Polyphenolic Mimetics
Certain compounds act as "exercise mimetics" by activating SIRT1 and FOXO pathways .
- Resveratrol: Activates SIRT1 deacetylase.
- Epicatechin: Stimulates Ca2+/CaM pathway (Dark Chocolate).
The Phosphorylation Switch
Gating enzyme activity via specific phosphorylation sites. The goal is to activate the accelerator and release the brake.
Ser1177 (Accelerator)
Phosphorylation here increases electron flux 2-3x.
Thr495 (Brake)
Phosphorylation here creates steric hindrance, blocking Calmodulin.
Cofactors & Inhibitors
Stabilizing the BH4 coupling mechanism and clearing the endogenous ADMA inhibitor.
BH4 Salvage
5-MTHF (Active Folate) chemically stabilizes BH4 and enhances binding. Vitamin C provides a "sparing effect" against oxidation .
ADMA Clearance
Taurine upregulates DDAH activity, the enzyme responsible for degrading ADMA. Reducing ROS is critical as DDAH is redox-sensitive .
Interactive Stack Builder
Select your current supplements to visualize which eNOS pathways you are targeting. Identify gaps in your protocol to ensure full enzymatic optimization.
1. Select Your Stack
Sildenafil (Viagra)
Blocks PDE5 enzyme from breaking down cGMP, extending the half-life of NO signaling.
Tadalafil (Cialis)
Blocks PDE5 enzyme with a 17.5 hour half-life, allowing for daily dosing.
Vardenafil (Levitra)
Highly selective PDE5 inhibitor, similar kinetics to Sildenafil but more potent.
Tamsulosin (Flomax)
Relaxes smooth muscle in the prostate and bladder neck. Less effect on blood pressure than non-selective agents.
Doxazosin (Cardura)
Relaxes smooth muscle in prostate and peripheral vasculature. Significant antihypertensive effect.
L-Citrulline
Bypasses hepatic first-pass metabolism; converts to Arginine in kidneys.
Beetroot Juice
Enterosalivary pathway: Nitrate → Nitrite → NO.
Dark Chocolate / Cocoa
Epicatechins stimulate eNOS phosphorylation via PI3K/Akt pathway.
Raw Garlic
Allicin degrades into polysulfides that donate H2S and activate eNOS.
5-MTHF (Active Folate)
Chemically stabilizes BH4 and promotes BH2 recycling via DHFR.
Nattokinase
Degrades fibrin directly and increases plasminogen activator, potentially reducing penile plaque formation.
Serrapeptase
Digests non-living tissue (fibrin, scar tissue) and reduces inflammation via bradykinin hydrolysis.
Vitamin C
Provides a 'sparing effect' on intracellular BH4 pools.
Taurine
Upregulates DDAH activity and CSE enzyme for H2S synthesis.
Resveratrol
Activates SIRT1/FOXO (transcription) and AMPK (phosphorylation).
Epicatechin (Cocoa Extract)
Stimulates Ca2+/CaM pathway to boost transcription.
Omega-3 (Fish Oil)
Enhances Akt-mediated phosphorylation of eNOS at Ser1177.
NAC (N-Acetyl Cysteine)
Reduces oxidative stress; Cysteine donor for H2S synthesis.
Pycnogenol (Pine Bark)
Increases eNOS expression and activity via endothelial protection.
Aged Garlic Extract
Polysulfides convert to H2S; S-allylcysteine protects BH4.
Pomegranate Juice
Punicalagins enhance eNOS bioactivity and reduce oxidative stress.
Quercetin
Upregulates eNOS gene expression via Ca2+/CaM pathway.
Curcumin (Turmeric)
Restores eNOS function in inflamed endothelium and lowers ADMA.
Mucuna Pruriens
Provides L-Dopa which crosses BBB to synthesize Dopamine.
P5P (Activated B6)
Cofactor for dopamine synthesis; inhibits pituitary prolactin.
Vitamin E
Works with B6 to lower serum prolactin levels.
L-Tyrosine
Precursor to L-Dopa and Dopamine.
Icariin (Horny Goat Weed)
Inhibits PDE5 (weaker than Viagra) and Rho-kinase (ROCK) to prevent fibrosis.
Gotu Kola (Centella Asiatica)
Modulates collagen production and improves venous tone.
Pentoxifylline
Non-selective PDE inhibitor; reduces TGF-beta mediated fibrosis.
Li-ESWT Device
Micro-trauma induces neovascularization and stem cell recruitment.
Vacuum Erection Device (VED)
Mechanically draws blood into corpora cavernosa to prevent hypoxia-induced fibrosis.
Red Light Therapy (LLLT)
Increases ATP production and NO release from cytochrome c oxidase.
BPC-157
Promotes angiogenesis and tendon/tissue repair (VEGF upregulation).
Melanotan II / PT-141
Agonist at melanocortin receptors (MC3/MC4) in the brain.
Spinach / Arugula
High dietary nitrate content for enterosalivary pathway.
Watermelon
Contains Citrulline, especially in the white rind.
Reverse Kegels
Reduces hypertonic pelvic floor tension that restricts blood flow.
Sprint Intervals
High intensity blood flow upregulates eNOS expression significantly.