Bradykinin: A Polypeptide that Regulates Blood Pressure

Do you know that hypertension was one of the earliest recorded medical disorders? It’s been affecting the health of humans for centuries, and today, high blood pressure is one of the leading causes of cardiovascular mortality. There’s a multitude of molecules that play a role in the regulation of blood pressure, including a member of the kinin family of peptides called bradykinin.

Bradykinin is a bioactive hormone that’s involved in a variety of physiological processes. It works as a potent pulmonary and systemic vasodilator, which means it plays a crucial role in controlling blood pressure. Beyond that, this peptide also works to avoid electrolyte imbalance and stimulates the body’s natural inflammatory response.

But too much bradykinin can be problematic, leading to low blood pressure, dry cough and even angioedema. The exact mechanisms of this powerful peptide can be difficult to understand, but hopefully this article gives you a better idea of its role in your body and possible side effects.

What Is Bradykinin? How Does It Work?

Bradykinin is an organic compound that causes the enlargement (or dilation) of blood cells. It’s a peptide, which means it’s made up of amino acids (nine, in this case) that are linked together.

Bradykinin is a vasodilator that widens our blood vessels. Vasodilators work by relaxing the smooth muscle cells that are within our vessel walls. By preventing the muscles from tightening and the vessel walls from narrowing, vasodilators allow blood to flow through the vessels more easily. This reduces the work on your heart, which doesn’t have to pump as hard, and therefore reduces blood pressure.

Ad

To put it simply, bradykinin allows for smooth muscle cells to become larger, which enables greater blood flow and lowers blood pressure.

There’s an entire class of drugs, called ACE inhibitors, that work to reduce blood pressure by inhibiting bradykinin degradation. ACE inhibitors are among the most prescribed antihypertensive drugs and remain the first choice in conventional medicine to treat cardiovascular disease, chronic heart failure, arrhythmias and a number of other conditions.

ACE (angiotensin converting enzyme) rapidly degrades the peptide, which only has a brief duration of action (plasma half-life of only 15—30 seconds). ACE breaks down over 95 percent of bradykinin in a single passage through the pulmonary circulation. This is why an ACE inhibitor is used to enhance the effects of bradykinin for cardiovascular health.

Bradykinin Benefits

Lowers blood pressure: Bradykinin is a vasodilator, which means that it works to reduce high blood pressure symptoms by relaxing smooth muscle cells within our vessel walls. For this reason, it’s particularly important in blood pressure regulation. Research shows that the kallikrein-kinin system comprises of peptides such as bradykinin, which exerts multiple physiologic actions that are important in the regulation of blood pressure.

Regulates water balance: The bradykinin system is involved in the mediation and modulation of the vasoconstrictor renin-angiotensin system, which is a group of hormones that act together to regulate blood pressure. Bradykinin also modulates the vasodilators prostaglandin, prostacyclin and nitric oxide in their ability to regulate sodium water balance, kidney and cardiac blood flow and blood pressure. It acts directly to inhibit sodium chloride and water reabsorption and supports the kidneys’ ability to respond to increases in dietary salt intake. This is how the peptide works to help regulate water and electrolyte balance.

Supports inflammatory response: In addition to its role in lowering blood pressure, this important peptide is also responsible for releasing inflammatory mediators. Kinins allow for the release of cytokines, which are needed to help us fight off infections and have a positive effect on our immune systems. Cytokines influence and interact with immune system cells, helping to regulate the body’s natural response to disease and infection. We need an optimal production of these proteins in order to maintain proper immune function.

Bradykinin Side Effects

Dry cough: Some patients taking ACE inhibitor drugs may experience a dry cough, which is due to increased levels of bradykinin. Bradykinin causes bronchoconstriction.

Angioedema: In severe cases, the elevation of bradykinin can result in angioedema, a condition that’s characterized by rapid swelling that can affect the respiratory mucosa. In some cases, angiodema may also cause temporary swelling of the tongue, mouth and lips. Angiodema is rare, occurring in 0.1 to 0.2 percent of patients taking ACE inhibitors that increase bradykinin levels. The condition causes airway swelling and obstruction due to the accumulation of bradykinin and fluid. Increased bradykinin causes the overactivation of B2 bradykinin receptors, which increases tissue permeability, vasodilation and edema.

Low blood pressure: The peptide works as a vasodilator and works to reduce blood pressure levels. But too much of the peptide can lead to hypotension. For some people taking ACE inhibitors, increased bradykinin may also cause dizziness or lightheadedness, which may result from blood pressure levels becoming too low.

Increased risk of cancer: According to a population-based cohort study published in BMJ, the use of ACE inhibitors was associated with an increased risk of lung cancer, and this association was particularly elevated among people using ACE inhibitors for more than five years. According to researchers, reports show that the accumulation of bradykinin in the lung may stimulate the growth of lung cancer. Plus, ACE inhibitors result in the accumulation of substance P, which is expressed in lung cancer tissue and may be linked to tumor proliferation and angiogenesis (the development of new blood vessels).

Which Cells Produce Bradykinin?

Bradykinin is produced by the kallikrein-kinin system. Kallikreins are proteinase enzymes that liberate vasoactive kinins. The two kallikreins that convert kininogens into bradykinin are plasma kallikrein, also known as Fletcher factor, and glandular kallikrein, which is known as tissue kallikrein.

The peptide is produced in the blood where it has potent but short-lived effects on capillary permeability and blood vessel dilation. Bradykinin is also released from mast cells from damaged tissues as a signal for pain and during asthma attacks. It plays an important role in the body’s natural inflammatory response and pain receptor stimulation. And it can even be released from the gut walls as a gastrointestinal vasodilator.

Histamine and Bradykinin

Histamine and bradykinin are both vasoactive agents that can cause swelling attacks associated with angioedema and vascular effects.  The actions of histamine are similar to those of bradykinin, as both are responsible for stimulating the body’s natural inflammatory and immune response.

Histamine is the main suspect mediator in allergic reactions. The compound is released by our cells in response to an injury or allergy. This inflammatory reaction causes the contraction of smooth muscle and the dilation of capillaries. Histamine receptors cause arteriolar vasodilation and increase capillary permeability. This can lead to increased blood flow and tissue swelling.

How to Control Levels

There are a number of natural bradykinin inhibitors that work to suppress the swelling that occurs when the peptide is released into the bloodstream and tissues. Here’s a quick breakdown of some known bradykinin inhibitors:

Ad

Bromelain: Bromelain is an enzyme that’s extracted from pineapple stems or cores. It’s valued for its anti-inflammatory and anti-swelling effects. It also has analgesic properties, which are believed to be the result of its direct influence on bradykinin and other pain mediators.

Aloe: Researchers found that aloe contains a material that may be able to break down bradykinin and inhibit its effects. This may explain the powerful anti-inflammatory properties of aloe.

Polyphenols: Scientists have found that polyphenols interact with bradykinin. Polyphenols are compounds that can be found in dark chocolate, red wine, blueberries and spinach. Studies display that polyphenolic molecules act upon the peptide’s structure and may inhibit its activity.

Final Thoughts

• Bradykinin is a vasodilator that widens our blood vessels. It works by relaxing the smooth muscle wells in our vessel walls and allowing blood to flow more easily.
• ACE inhibitors are commonly prescribed to inhibit bradykinin degradation and lower blood pressure levels. These are the most prescribed antihypertensive drugs used in conventional medicine.
• The peptide also plays an important role in the body’s natural inflammatory response, helping it to fight infections and react to injuries.
• Too much of this hormone can lead to low blood pressure (causing symptoms like dizziness and lightheadedness), dry cough, angioedema (although this is rare) and maybe even an increased risk of cancer.