Biochemistry of Sexual Arousal

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Nitric oxide is the Neurotransmitter of Sex. 
The entire human body relies on two critical gasses to survive and thrive. One is oxygen, which we get from the air we breathe. But to move oxygen around into tissue more than 2 mm thick, we need blood flow. To get blood to flow through small blood vessels, our body manufactures a gas called Nitric Oxide which relaxes blood vessels.
Because sexual arousal relies on blood flow and engorgement, nitric oxide

  • production,
  • utility and
  • recycling is critically central to the biochemistry of sex. Start at the left side:

The Making of NO
The protein L-arginine is at the beginning of nitric oxide (NO) production. L-arginine is manufactured in the liver, but the total body supply is supplemented with food proteins. Our bodies use L-arginine continuously to make NO. To do that, our cells need to have other important things available, like calcium and Vitamin D, and specific catalyst enzymes to make the equation go faster. 
To make NO, L-arginine is converted to L-citrulline (another protein), which can again be recycled into L-arginine. However, if the body needs to slow this equation down a build up of L-citruline (and NO) will also act as brakes on the system. This happens when too much L-citruline is available, too much inflammation occurs, or the calcium/calmodulin complex is used up or not available.

Make Love, not War.
Mammals make nitric oxide (NO) in three ways. Two we use for sexual arousal and other protective/healing functions. The third is a primitive inflammatory system whereby the body attacks outside invaders, and sometimes, by mistake, itself. 
The three systems are:

  1. Inside Blood Vessels: Stretching, patting, rubbing or twisting small blood vessels causes nitric oxide to be made right at the inside of the blood vessel (endothelium). Nitric oxide chemically converts guanylyl cyclase into cyclic guanosine monophosphate (cGMP) which relaxes (vasodilates) the blood vessel smooth muscle and allows more blood to flow through. The enzyme responsible for this NO production is called “endothelial Nitric Oxide Synthase” or eNOS.
  2. At Nerve Terminals: Nitrergic nerves involved in sexual arousal produce NO to communicate to blood vessels. This portion of the parasympathetic system has end terminals that make NO from L-arginine when they get an electrical impulse. The particular enzyme responsible for production is called “neural Nitric Oxide Synthase” or nNOS.
  3. Because They Can: Evolutionary biologists feel that the original use of NO wasn’t for sexual arousal or communication, but to stomp out dangerous bacterial invasion. In an early form of immune system defense, white blood cells called macrophages produce free radicals to halt bacterial infections. This on-demand production by of NO and Oxygen radicals is very destructive. The enzyme responsible for production is called “inducible Nitric Oxide Synthase” or iNOS

For sexual purposes, nitric oxide production is the key component in starting the vasodilation cascade. Without nitric oxide, the cascade will not progress and vasodilation will not occur. Once the cascade has begun, it is brought to an end by PhosphoDiEsterase type 5 (PDE-5). Medications like sildenafil (Viagra) are PDE-5 Inhibitors. They keep the cascade from ending and allow blood flow and engorgement to continue once it starts. PDE-5 Inhibitors do not start the engorgement cascade itself, nitric oxide does. 

Love is healthier for you.
Endothelial NOS and nNOS tools of love, while iNOS a tool of war. Making love is much healthier for you. Generally, iNOS-related NO is dangerous and hard to control biologically. Inducible NOS has helpful biologic roles such as a natural part of the mechanism of uterine contractions during labor and delivery, and protection from infection. However, iNOS-related NO production is dangerously associated with common illness of Western lifestyles such as diabetes, cancer and heart disease. 
Ultimately, we need NO for health, but we absolutely need an underlying antioxidant diet and routine exercise to destroy and mop up stray free radicals. Free radicals are made all of the time--which is fine. We just need to take care of the systems that vacuum up what’s left over. Mom was right: clean up your room, and love is good.

Calcium matters, sometimes.
Medically, it’s important to know that the eNOS and nNOS systems share a common production pathway dependent on calcium movement (L-type channels), and cGMP. Interestingly, the iNOS system is calcium and cGMP independent because when the immune system needs production, it’s not useful to be hampered by low calcium blood levels. Because of this manipulation of these three systems are differently effected by foods, herbs and drugs. 

For example, medications called calcium channel blockers help hold calcium inside blood vessel cells, and brings down blood pressure by enabling NO-dependent vasodilation to occur. Conversely, calcium channel blockers do not have any effect on iNOS-related NO production, because that production is calcium independent.

Everyone: at the same time.
The key to understanding the sexual and medical implications of nitric oxide begins with the realization that these three systems function all at the same time. Consider what Goldilocks faced when she sat down to eat her porridge: some was too hot, some too cold, while some was just right. We have the same basic situation with NO:

  1. Just right: when NO is produced in enough quantity to produce healthy and variable blood flow, everything is just right. Our bodies function best when some is produced, and then flushed away. Because the capacity for sexual arousal demonstrates the perfect production of NO, sexual arousal is a key indicator of peak physical health.
  2. Too hot: when too much NO is being produced, inflammation will occur. Abundant free radicals destroy--that’s all they do. This explains why underlying inflammation due to metabolic disorders (high blood sugar, etc.) is so dangerous: if more NO is made for a sexually arousing episode, and it runs into pre-existing inflammatory NO, a destructive party will begin. It also explains some of the dangerous side effects of medications like Viagra (PDE5 inhibitors): if NO’s action continues in the face of underlying inflammation, destruction ensues. The medication essentially prolongs the effect of NO, and this can harm nerves in the eye (blue vision), and the heart (heart pains or angina). If the underlying inflammation is addressed through exercise and antioxidant diets, Viva Viagra they say. And skip the bacon: the nitrates and nitrites used to kill bacteria on preserved meats adds the N- to NO production. Just eat the porridge.
  3. Too cold: Not being able to produce NO means that important vasodilation ceases, and blood flow will be poor. Over the long term, poor blood flow signals cells to die. Therefore, diets low in L-arginine, or inflammatory (high sugar) diets will leave your body suffering, nerves dying, and put sexual dysfunction in the future.

We agree with Goldilocks: just right is perfect.

If you have a burning desire to understand more about sexual arousal through my adaptation of the fairy tale: Goldilocks and the Three Bears, click the side bar article. It's detailed, geeky, but kind of fun to read.

 

Take Care,

Dr. Myrtle