We spend a lot of time concerned over topline, hoof balance, and gut health. But there is a molecular superhero working silently inside your horse’s blood vessels that controls nearly everything about their athletic potential and recovery.
It’s called eNOS (Endothelial Nitric Oxide Synthase).
◆︎ What is eNOS, and Why Should I Care?
eNOS is the "gatekeeper" of your horse’s cardiovascular system. The lining of your horse's blood vessels, the endothelium, isn't just a smooth pipe. The muscles in the blood vessels are active in dilating or constricting.
eNOS converts L-arginine to nitric oxide.
The nitric oxide diffuses from the endothelium to the smooth muscle in the blood vessel, causing vasodilation.
This helps control blood pressure, prevents clots, and reduces inflammation. It is also implicated in the adequate blood flow to the hooves. The horse’s vascular tone is appropriate at all points in time, whether the horse is relaxing under a tree or galloping across the field.
◆︎ eNOS is both the Hero and the Villain
The Hero: eNOS needs to couple to BH4 to produce nitric oxide. BH4 is tetrahydrobiopterin. Nitric oxide affects the blood vessels, but also acts as an anti-oxidant.
The Villan: When the horse is under severe oxidative stress, or has insufficient BH4, eNOS becomes uncoupled. This uncoupling produces superoxide instead of nitric oxide. Superoxide is a toxic molecule, which damages proteins and DNA.
◆︎ How to increase your horse’s eNOS
Exercise: Increased blood flow due to exercise increases the activity of eNOS. This is accomplished by creating shear stress within the blood vessels.
Although exercise is one of the best ways to increase eNOS in the horse, when your horse is debilitated or laminitic,the ability to exercise may be limited.
➡ Precursors and BH4:
Arginine supplementation: AAKG (arginine alpha ketoglutarate) is a bioactive form of arginine. Arginine is a precursor to nitric oxide.
Vitamin C: Helps maintain levels of BH4, which in turn, helps prevent eNOS from uncoupling.
CoQ10: Like vitamin C, CoQ10 helps BH4 stay coupled.
➡ Supplements that increase activation of the eNOS pathway:
Jiaogulan: Jiaogulan is unique because it stimulates the direct release of nitric oxide from endothelial cells.
Mov-Ease: works by activating the PI3K/Akt pathway. This is a specific cellular signaling chain that leads to the activation of eNOS. It essentially "switches on" the enzyme to produce more nitric oxide.
Quercetin: is a dual-action helper. First, it creates a rapid increase in intracellular calcium, which stimulates eNOS to produce NO. Second, it acts as a scavenger for superoxide, preventing the dangerous "uncoupling" of eNOS that leads to vascular damage.
Resveratrol: It directly upregulates the VEGF-B/AMPK/eNOS signaling pathway. Essentially, it turns the "volume knob" up on the signals that tells eNOS to increase nitric oxide.
◆︎ Veterinary care:
There are times that nutraceuticals or herbs will not be sufficient (ie, foals with pulmonary hypertension) and veterinary care is necessary for the best outcome. It is important to involve your veterinarian to ensure that your horse has the best possible care.
We do the best we can for our horses. Understanding our horse's needsis a part of that.
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Disclaimer: Statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease or health condition.
©Joan Kulifay, MSc. 2026