Bradykinin

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Questions and Answers

What is one of the primary mechanisms by which bradykinins exert their cardioprotective effects?

Stimulation of tissue plasminogen activator (tPA) release (correct)

Inhibition of myocardial cell apoptosis

Stimulation of inflammatory cytokine release

Increase in heart rate and contractility

Which neuropeptide is primarily released by sensory neurons in response to pain stimulation?

Cholecystokinin

Substance P (correct)

Neurokinin B

Calcitonin gene-related peptide

What effect do kinins have on renal function?

Increase sodium reabsorption

Decrease in renal blood flow

Causing natriuresis (correct)

Inducing renal ischemia

Which of the following symptoms is characteristic of a 'wheal and flare' response induced by bradykinins?

Redness and local swelling Signup and view all the answers

In patients with hereditary angioedema, what triggers the recurrent episodes of angioedema?

Increased formation of bradykinin Signup and view all the answers

What is a common adverse effect associated with the use of ACE inhibitors?

Chronic, non-productive cough Signup and view all the answers

Icatibant is classified as which type of drug?

Selective B2 receptor antagonist Signup and view all the answers

Which condition might be exacerbated by bradykinin causing bronchospasm?

Asthma Signup and view all the answers

What role do kinins play in the inflammatory process?

Stimulate vasodilation Signup and view all the answers

What is the investigational focus of fasitibant?

Managing pain and inflammation in knee osteoarthritis Signup and view all the answers

What is the primary location where kallikreins are found?

Plasma and various tissues Signup and view all the answers

Which type of kininogen is a substrate for tissue kallikrein?

Low-molecular weight kininogen Signup and view all the answers

What type of receptors primarily mediate the effects of bradykinin?

G-protein-coupled receptors (GPCRs) Signup and view all the answers

Which receptor is most commonly expressed in normal tissues and mediates the effects of bradykinin?

B2 receptor Signup and view all the answers

What is NOT a function attributed to bradykinin?

Inducing apoptosis Signup and view all the answers

Which of the following is a potent mediator stimulated by bradykinin's action?

Nitric oxide (NO) Signup and view all the answers

What is the primary role of the B1 receptor in relation to bradykinin?

Triggering inflammatory responses Signup and view all the answers

Which type of bradykinin is identified as Lys-bradykinin?

Kallidin Signup and view all the answers

Which of the following effects is NOT produced by bradykinin?

Increased cardiac output Signup and view all the answers

What is quickly responsible for the degradation of bradykinin in the body?

Kininases and ACE Signup and view all the answers

Study Notes

Bradykinin

Bradykinin is a peptide that acts as an autacoid, influencing various bodily functions.
Bradykinin’s activity is primarily stimulated by potent mediators: prostaglandins, nitric oxide (NO), and endothelium-derived hyperpolarizing factors (EDHF).

Bradykinin: Biosynthesis

Kallikreins are serine proteases found in plasma and tissues.
They convert kininogen into kinin.
There are two forms of kininogen: high-molecular weight kininogen (found in plasma) and low-molecular weight kininogen (found in tissues).
The two major types of kinins in humans are bradykinin and Lys-bradykinin (Kallidin).
Kinins are rapidly degraded by kininases and angiotensin-converting enzyme (ACE).

Bradykinin Receptors

Bradykinin receptors are G protein-coupled receptors (GPCRs).
The B2 receptor is found in most normal tissues.
It binds to bradykinin and kallidin, mediating most of bradykinin's effects.
The B1 receptor is triggered by inflammatory mediators and is active in inflammatory conditions.

Bradykinin Effects

Cardiovascular:
- Bradykinin causes vasodilation by activating its B2 receptor on endothelial cells, triggering the release of NO and vasodilator prostaglandins such as PGE2 and PGI2.
- Bradykinin has cardioprotective effects, including anti-proliferative effects.
- It protects the heart against ischemia and reperfusion injury.
- It helps prevent myocardial infarction and stroke through stimulation of tissue plasminogen activator (tPA) release.
Pain:
- Bradykinin stimulates sensory neurons and provokes the release of neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide.
Inflammation:
- Bradykinin causes vasodilation and increased permeability in the microcirculation.
- It increases hydrostatic pressure gradient, leading to edema.
- It stimulates nerve endings.
- These effects result in a "wheal and flare" response to intradermal injection of bradykinin: redness, local heat, swelling, and pain.
Kidney:
- Bradykinin increases renal blood flow due to vasodilation.
- It causes natriuresis by inhibiting sodium reabsorption.
Non-vascular Smooth Muscle:
- Bradykinin causes contraction of intestinal, urinary, and bronchial smooth muscle.
- It may be implicated in allergic airway disorders such as asthma and rhinitis. Bradykinin causes bronchospasm in asthmatic patients but not in normal individuals.
Hereditary Angioedema:
- This rare genetic disorder results in increased activation of kallikrein and bradykinin formation.
- Increased vascular permeability and other actions lead to recurring episodes of angioedema in the airways, gastrointestinal tract, extremities, and genitalia.

Drugs that Target Bradykinin

ACE Inhibitors (ACEIs):
- ACEIs block the conversion of angiotensin I (ANGI) to angiotensin II (ANGII) and inhibit bradykinin degradation.
- Increased bradykinin may contribute to beneficial protective effects, but it can also cause adverse effects.
- Common side effect: Chronic, non-productive cough.
- Rare side effect: Angioedema.
Kinin Receptor Antagonists:
- Icatibant:
  - A selective B2 receptor antagonist approved for hereditary angioedema-related swelling.
- Fasitibant:
  - Under investigation for intra-articular injection for knee osteoarthritis to alleviate inflammation and pain through bradykinin pathway modulation.