Nitric oxide supplements are some of the most highly sought after pre workout supplements on the market. With promises of bigger, nastier pumps, skin-splitting veins, and filled out muscles, it’s easy to see the allure of pump pre workouts.
There’s a reason Arnold compared getting a raging muscle pump to an orgasm -- the feeling is simply euphoric!
But, with so many pre workouts out there claiming to increase pumps and vascularity, it's incredibly easy to get bogged down in selecting a pump pre workout that actually delivers the results advertised on the bottle. Not only must a properly formulated pump pre workout contain clinically proven ingredients in their efficacious doses, but they also have to combine those ingredients properly.
As you’ll see, more isn’t always better when it comes to maximizing pumps and vasodilation in your pre workout.
How Nitric Oxide Works?
You probably know by now that nitric oxide plays a key role in your ability to get massive pumps and gorging veins while training, but have you ever given thought to how exactly nitric oxide does what it does?
Most likely not, but in order to understand how a properly formulated pump pre workout should look, it’s important that you understand the underlying mechanisms of what goes into getting a hard, dense muscle pump during training.
So, let’s get a little closer to this “money molecule” that is nitric oxide and see how it works.
Nitric Oxide → Vasodilation
Nitric oxide is generated from the amino acid L-arginine by the enzymatic action of nitric oxide synthase (NOS). In blood vessels (endothelial tissue), the enzyme endothelial nitric oxide synthase (eNOS) produces nitric oxide. FYI, this is the type of nitric oxide we want for increasing vasodilation and pumps.
There are two other forms of nitric oxide synthase: neural NOS (nNOS) and inducible NOS (iNOS), but those exert very different actions in the body not pertaining to muscle pumps, so we’ll save the discussion of the differences between NOS isomers for a separate article. For now, just realize that we’re interested in eNOS and maximizing its effects in the blood vessels surrounding muscle tissue.
So, once nitric oxide synthesis is initiating, it promotes vasodilation (widening of blood vessels) through a myriad of physiological events that result in the relaxation of smooth muscle cells that line the veins and arteries. While the exact mechanisms are a bit complex, we’ll try to keep it as simple and straightforward as possible.
How Nitric Oxide Causes Vasodilation
Nitric oxide gas released from nitrosothiols present in endothelial cells diffuses into smooth muscle cells lining small blood vessels
Upon entering the smooth muscle cell, nitric oxide binds to the enzyme guanylate cyclase, leading to activation of guanylate cyclase
Guanylate cyclase severs two phosphate groups from another molecule called guanosine triphosphate that leads to the formation of cyclic guanosine monophosphate (cGMP).
cGMP is then used to phosphorylate (add a phosphate group) specific proteins present in smooth muscle, namely myosin
Once these proteins are phosphorylated, myosin relaxes smooth muscle cells, which leads to vasodilation of the blood vessel that was initially exposed to nitric oxide.
Sounds pretty complicated doesn’t it?
Well, that’s because the human body is incredibly complex, but the important takeaway for you reading this is that increasing nitric oxide is a good thing, but as much as you may want to increasingly boost nitric oxide production, it’s cGMP that ultimately governs how much of that nitric oxide is actually put to use. Anything that can prevent the breakdown of cGMP is a must have if you’re looking to maximize nitric oxide-based vasodilation. This is what makes certain pharmaceuticals, such as Viagra, incredibly powerful -- they inhibit the breakdown of cGMP.
So, when you’re looking to maximize your vasodilation and muscle pumps during your workouts, you want ingredients that increase nitric oxide production as well as ones that increase cGMP levels or prevent its breakdown.
Additionally, there’s something else you need to realize…
Nitric Oxide has an incredibly short half-life!
Once formed, nitric oxide only has a half-life of approximately 2 milliseconds (ms). This is due in large part to the superoxide anion which loves it some nitric oxide, which means that the superoxide anion ultimately reduces nitric oxide bioavailability. On top of that, there’s also the matter of arginase -- the enzyme that breaks down arginine. In case you forgot, L-arginine is the amino acid that kickstarts the whole nitric oxide production process, and if it’s getting gobbled up by arginase before it has a chance to start producing nitric oxide, you can kiss your gorging veins and muscle pumps goodbye!
So, when looking to get those epic nitric oxide-fueled pumps during your workout, you need to:
Increase plasma levels of arginine
Inhibit arginase activity
Increase cGMP (or prevent its breakdown)
As if that wasn’t enough to worry about, we also need to guard against vasoconstriction (constriction or narrowing of blood vessels), which reduces blood flow and increases blood pressure, not something you want during a hard workout. Vasoconstriction can happen as a result of using certain decongestants, antihistamines, or stimulants, or the body can naturally restrict vasodilation due to the actions of the vasoconstricting enzyme angiotensin converting enzyme (ACE).
This now adds a fourth factor to consider when trying to maximize vasodilation -- inhibition of ACE.
If your head is spinning for all of these knowledge bombs, just realize so are a vast majority of the companies producing the so-called “best” pump pre workout, which is why so many pump pre workouts cram redundant ingredients on top of each other (i.e. L-Citrulline + Nitrosigine + Arginine AKG, etc.)
They’ve made the mistake of thinking that endlessly upping the number of nitric oxide boosting compounds will lead to bigger, nastier muscle pumps, but what they fail to consider is the fact that each smooth muscle cell has a limited number of guanylate cyclase enzymes, and once all of those enzymes are activated, adding more additional nitric oxide on top of that isn’t going to further improve vasodilation, blood flow, or pumps.
Fortunately, Primeval Labs has done the research and formulate a pump pre workout that addresses muscle pumps from a multitude of angles to deliver a product that not only increases nitric oxide, but prevents breakdown of arginine, and combats vasoconstriction.
Mega Pre -- The True King of Pumps!
Mega Pre is the consummate vasodilation pre workout that includes:
6 grams L-Citrulline to increase plasma arginine levels and fuel nitric oxide production
300mg L-Norvaline to inhibit arginase and maximize levels of L-Arginine
254mg VasoDrive-AP to inhibit ACE and combat vasoconstriction
But that’s not all, Mega Pre also includes several other pump enhancing supplements in the form of:
2g GlycerPump for increased cellular hydration and “water-based” pumps
1g Choline bitartrate to protect the body’s natural reserves of nitric oxide
As you can see, Mega Pre takes a multi-tiered approach to supporting, protecting, and encouraging vasodilation. This leads to a pump pre workout that delivers stronger, longer-lasting pumps as well as superior performance and gains in your workouts.
Don’t fall for the hype of other alleged pump pre workouts. When you’re looking for the best of the best, the only choice for a true-blue vasodilation pump pre workout is Primeval Labs Mega Pre!
Singh RJ, Hogg N, Joseph J, Kalyanaraman B. Mechanism of Nitric Oxide Release from S-Nitrosothiols. J Biol Chem . 1996;271(31):18596-18603. doi:10.1074/jbc.271.31.18596
Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. European Heart Journal. 2012;33(7):829-837. doi:10.1093/eurheartj/ehr304.
Thomas DD, Liu X, Kantrow SP, Lancaster JR. The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O2. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(1):355-360.
Pokrovskiy MV, Korokin MV, Tsepeleva SA, et al. Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction. International Journal of Hypertension. 2011;2011:515047. doi:10.4061/2011/515047.
FitzGerald RJ, Meisel H. Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme. Br J Nutr. 2000;84 Suppl 1:S33-37.
Hirota T, Ohki K, Kawagishi R, et al. Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: contribution of the inhibitory action of angiotensin-converting enzyme. Hypertension research : official journal of the Japanese Society of Hypertension. 2007;30(6):489-496.
Fekete ÁA, Givens DI, Lovegrove JA. Casein-Derived Lactotripeptides Reduce Systolic and Diastolic Blood Pressure in a Meta-Analysis of Randomised Clinical Trials. Nutrients. 2015;7(1):659-681.