Kinins, such as bradykinin and kallidin, play key roles in regulating blood pressure, inflammation, and pain sensation. This slideshare delves into the intricate mechanisms by which kinins exert their effects.

1. The Physiological and Pathophysiological
Role of
KININS
Anagha R Anil
MPharm Pharmacology

2. Contents
• Kinins
• Synthesis
• Roles of Kinins
• Receptors and their function
• Physiological & Pathophysiological Role of Kinins
• Research Article

3. KININS
Class of polypeptides that belongs to the Autocoid family.
Major Site of Action:
● Cardiovascular System
● Renal System
● Site of Injury
Bradykinin
Kallidin

4. Synthesis
Kininogens
HMW
Kininogens
LMW
Kininogens
Bradykinin
Kallidin
Plasma
Kallikrein
Tissue
Kallikrein
desArg9-bradykinin
desArg10-kallidin
Bradykinin
(inactive)
Kallidin
(inactive)
Kininase Type II
(dipeptidylpeptidase ACE + neutral endopeptidase)
Kininase Type II
(dipeptidylpeptidase ACE + neutral endopeptidase)
Agonist of B2 Receptor
Agonist of B1 Receptor
Inactive
peptide
Kinin-Kallikrein System

5. Intracellular Signaling
● ⬆️ Intracellular Ca2+ stimulates immune cells and inflammatory mediators such
as prostaglandins, cytokines, leukotrienes and nitric oxide

6. Role of Kinins
 Potent vasodilators
 Regulate blood pressure
 Stimulate the release of Prostacyclin and Nitric Oxide
 Regulation of electrolyte balance and fluid homeostasis (↑renal blood flow)
 Cause pain and inflammation by sensitizing nociceptors (pain receptors)
 Promotes the release of inflammatory mediators (prostaglandins, cytokines,
leukotrienes and nitric oxide)
 Tissue repair (angiogenesis)
 Therapeutic implication (ACE Inhibitors ↑ Bradykinin and reduce BP)

7. Receptors
Classification
(based on receptors)
B1(Gq)
Bradykinin
Kallidin
B2(Gq)
des-Arg9-BK
Des-Arg10-Kallidin

8. Physiological & Pathophysiological
Role of Kinins
• Excessive kinin activity may contribute
to vasodilatory shock.
• Vasodilation
Bradykinin binds to endothelial cells –
release of NO – vasodilation
• Increase in Capillary Permeability
To allow flow of fluids, nutrients, and
immune cells to site of injury
1. Cardiovascular System

9. • Edema
Excessive kinin activity can lead to edema
(swelling) by increasing capillary permeability.
Inflammatory skin conditions, such as urticaria
and angioedema, are associated with kinin-
mediated vasodilation and increased
permeability.
• Pain and Sensitization
Binds to B1 and B2 receptors on sensory
nerve endings - increased perception of
pain and heat
• Inflammation
Promote inflammation by inducing the
release of pro-inflammatory cytokines
and chemokines, which attract white
blood cells (leukocytes) to sites of
infection or injury, aiding in the immune
response
2. Inflammatory System
Urticaria
Angioedema

10. • Dysregulation of renal function in
diabetic nephropathy due to altered
kinin levels.
• Bronchoconstriction
activate B2 receptors on smooth muscle
cells in the airways
3. Respiratory System
• Regulation of renal blood flow and
filtration.
Promotes vasodilation and increases
capillary permeability, thus influence the
glomerular filtration rate (GFR) and renal
blood flow.
This can help maintain appropriate
kidney function.
4. Renal System
• Increased bradykinin can also lead to
dry, persistent cough, which is a well-
known side effect of ACE inhibitors in
some patients

11. • Excessive kinin-induced contraction
may contribute to conditions like
gastroesophageal reflux disease
(GERD)
• Inflammatory Bowel Disease (IBD):
Kinins have been implicated in the
pathophysiology of IBD, such as
Crohn's disease and ulcerative colitis.
They contribute to inflammation in the
gut by attracting immune cells and
promoting cytokine release.
• Smooth Muscle Contraction
Kinins stimulate smooth muscle
contraction, which can influence the
motility of the digestive
system(peristalsis).
• Digestive Secretions
Activation of B2 receptors on the
secretory cells within the gastric mucosa
and pancreatic acini
• Blood Flow Regulation
Increased blood flow helps deliver
oxygen and nutrients to the digestive
organs.
5. Gastrointestinal System

12. Research Articles
• The study included 27 healthy control (HC)
subjects and 63 severe COVID-19 (COV)
pneumonia patients.
• Patients with COVID-19 had elevated plasma
concentrations of HK (High Molecular Weight
Kininogen)
• Reduced levels of Bradykinin
• Increased levels of BK1-8(metabolite)
CONCLUSION
• A ROC curve analysis indicated that BK1-8
levels could be used as a potential marker for
ICU admission with an accuracy of 92.9%.

13. Thank You!