Part 2 of 3: The Hypertension Series

Last week, we explored the significance of hypertension as a public health epidemic and started talking about what influences the development of hypertension. In this second installment of our series, we will discuss how hypertension can cause complications in our bodies, starting with biological pathways. 

Think of blood pressure biochemical pathways as runners in a relay race. Nearly all of them begin with a hormone binding to a receptor. This is the horn that signals the first runner to take off. Then, the receptor is induced to begin a series of intracellular changes that lead to what biochemists call a “signaling cascade,” as molecules activated by the receptor move on to activate more molecules. Think of this as relay runners passing the baton to each other. 

The endgame of a signaling cascade is to bring about some kind of meaningful change in cellular activity, which could be anything from activating a protein kinase (a potent “supercharger” of cellular activity) to affecting gene expression. At that point, the final runner has crossed the finish line. These pathways send messages through our blood to different tissues and organs, telling them when to perform a specific task to establish a balance in our bodies.

The Relay Race

Many of the molecules that initiate signaling cascades fall into the broad category of hormones, which are long-distance signaling molecules produced by glands located throughout the body. The hormones in our bodies that control blood pressure act by regulating vessel diameter or controlling blood volume. Below is a list of hormones that increase our blood pressure:

  1. Norepinephrine
    • Norepinephrine is usually released in response to stress, where our body is preparing to fight or run. Therefore, this hormone acts as part of an involuntary pathway involved in increasing our heart rate, glucose metabolism, pupil dilation, urinary bladder contraction and so on. It decreases the diameter of the blood vessel, which increases resistance and blood pressure.

  2. Renin-Angiotensin System
    • Renin release depends on the kidneys, which initiates the production of angiotensin II. 
    • Angiotensin II has many effects, including 
      1. Stimulating sympathetic nervous system activity (fight/flight system)
      2. Promoting reabsorption of sodium and chloride in the kidneys, which is followed by an increase in water reabsorption 
      3. Stimulation of the adrenal cortex to increase production of aldosterone, which in turn increases water retention in the kidneys 
      4. Stimulation of arteriolar vasoconstriction (tightening of blood vessel diameter)
      5. Stimulation of antidiuretic hormone (ADH) release from the posterior pituitary gland

Each of these effects lead to elevated blood pressure. For example, the stimulation of sympathetic activity promotes an elevated heart rate,  while an increase in kidney water retention by aldosterone will increase blood volume, which can elevate blood pressure. Similarly, ADH also increases water reabsorption in the kidney tubule system to increase blood volume and pressure.

The next two biomolecules play a regulatory role by decreasing our blood pressure. The reason it is important to address them is because any malfunction in their secretion can lead to hypertension.

  1. Atrial Natriuretic Peptide (ANP)

    • ANP is released in response to the stretch of a cardiac cell in the heart, which occurs due to high blood pressure and plays an important role in vasodilation, which leads to a decrease in resistance and blood pressure.
  2. Nitric Oxide (NO)
    • Nitric oxide is a gas produced by the enzyme nitric oxide synthase, which makes it special right off the bat because there aren’t many other gasses that can claim to be neurotransmitters. Various external factors, along with blood flow shear stress (literally blood pressing against blood vessels like water presses against the inner walls of a hose), can activate receptors that stimulate the production of NO. It initiates a pathway that culminates in the inhibition of calcium channels in vascular smooth muscle cells, thereby promoting vasodilation and reducing blood pressure.

For a hormone to act, it needs a signal from the brain telling it what to do. Enter the Cardiovascular Center, which is the processing center that sends out a plethora of nerve impulses to the heart or blood vessels to adjust its cardiac output or diameter. However, hormones are often slow-acting – so instead of waiting around for a hormone to decrease blood pressure, our bodies compensate by controlling other bodily functions that can mitigate the effects of elevated blood pressure. 

One example: baroreceptors.These are stretch receptors located on our blood vessels that respond to pressure-induced stretching by decreasing heart rate. This is known as the Baroreceptor reflex or Baroreflex. You might wonder – how does decreasing heart rate regulate our blood pressure? Since heart rate measures the number of times a heart beats per minute, you can expect a lower blood volume to result from a decrease in heart rate. 

The Environmental Triggers

Now that you’re familiar with most of the players involved in blood pressure regulation, let’s look at how particulate matter interacts with them and disrupts our homeostatic mechanisms.

The effect of PM on our bodily processes is not straightforward by any means. It would be so much easier to classify its effects if it interfered with only one pathway. Unfortunately, PM not only interferes with pathways that increase blood pressure, but also with pathways that decrease blood pressure simultaneously, thereby producing unpredictable outcomes.

Many times, with the help of our bodies’ default self-regulatory pathways, the erratic changes can be controlled. Yet, as you age and are continuously exposed to PM, these slight alterations may pose as risk factors for the development of atherosclerosis, a disease characterized by the deposition of plaques or fatty materials on the inner walls of our arteries. This disease often begins with damage to the endothelium wall (the wall lining our blood vessels), which occurs as a result of excessive inflammation.

Inflammation is a protective response to foreign materials that enter our bodies, which is beneficial for us. However, nothing in excess is good for our bodily reactions. The steps that lead to the inflammatory process begin with the deposition of inhaled particles on our respiratory tracts. This triggers the production of Reactive Oxygen Species (ROS) (Araujo, 2009). 

While oxygen is fundamental to starting a fire, whether it be a quick process of turning on the stove or the slow process of breaking down food in our bodies, all fires come at a cost. Oxygen that is not creating energy ends up damaging cells, so when ROS levels become too high, our cells begin to experience intense discomfort that could lead to cell death. No wonder you are often advised to consume foods that are enriched with antioxidant properties! 

The overproduction of ROS during prolonged exposure to PM is responsible for the constant circulation of overworked white blood cells in our bloodstreams, attempting to capture toxic particles that have evaded the mechanical defenses of the respiratory tract. The continuous activation of our immune systems ultimately leads to blood vessel damage and promotes the growth of plaques. It is speculated that these events contribute to future vascular events, such as the stiffening and narrowing of arteries, reduced blood flow and decreased supply of oxygen and nutrients to cells and tissues, all associated with the onset of atherosclerosis (Tamagawa et al, 2008).

Airway injury, or damage to lung epithelial cells as a consequence of PM exposure, sends stress signals to our brain, which immediately activates the Sympathetic Nervous System (SNS). As mentioned earlier, this system acts like a gas pedal of a car, triggering a bunch of physiological variables that are out of our conscious control such as increasing heart rate, dilating pupil diameter, elevating blood pressure, slowing down digestive rate, and so on. The Renin-Angiotensin pathway is also overstimulated during PM exposure, which in turn increases the activity of the SNS, creating a vicious cycle that amplifies the negative effects so many times more.

It is fascinating to see how changes at the molecular level can have huge macro impacts on our bodies, testing the limits of its security and safety systems. So far, we have explored the external factors that bring about hypertension. But what about the internal factors? More specifically, what might genetic changes to specific parts of these biochemical pathways imply for hypertension? Find out more next week!

Citations:

Araujo, J. and Nel, A. (2009). Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress. Particle and Fibre Toxicology, 6(1), p.24.

Tamagawa, E., Bai, N., Morimoto, K., Gray, C., Mui, T., Yatera, K., Zhang, X., Xing, L., Li, Y., Laher, I., Sin, D., Man, S. and van Eeden, S. (2008). Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction. American Journal of Physiology-Lung Cellular and Molecular Physiology, 295(1), pp.L79-L85.