Plasma Kinins in animals

Plasma Kinins in animals are local mediators of pain and inflammation. The kinins are a family of small peptide molecules, which include- Bradykinin and Kallidin.

Tissue damage, allergic reactions, viral infections and inflammatory events activate a series of proteolytic reactions and liberate bradykinin and kallidin. These agents act locally to produce pain, vasodilatation, increased vascular permeability and synthesize prostaglandins.

When urine was injected intravenously there was a reduction in blood pressure. Same response was noticed when saliva, plasma and a variety of tissues.

Pancreas was identified as the organ with rich source of this blood pressure lowering agent. Hence, they were termed as Kallikreins.

Plasma kinins are polypeptides that split off from a plasma globulin kininogen by the action of specific enzymes kallikreins. It was noticed that trypsin and certain snake venoms acted on plasma globulin to produce a substance that lowered blood pressure and caused a slow developing contraction of the gut. Because of this slow response this substance was termed as bradykinin (brady – slow, kinin – to move).

kallidin, a decapeptide was identified with almost similar actions. Thereafter a number of polypeptides with similar pharmacological actions were identified in nature. All these substances together were termed as kinins. Bradykinin and kallidin were termed as plasma kinins.

Synthesis of kinins

Kinins are produced in response to tissue damage. Tissue damage causes the activation of Hageman factor, which is involved in the clotting mechanism.

Hageman factor converts plasma prekallikrien to plasma kallikrein. Kallikreins are enzymes, which break down kininogens (the precursors of kinins). There are 2 forms of kallikreins: Plasma kallikrein and Tissue kallikrein (found in the pancreas).

Plasma kallikrein converts high molcular weight kininogen to bradykinin. Tissue kallikrein converts low molecular weight kininogen to kallidin.

Metabolism of kinins

Two types of enzymes metabolize kinins- Aminopeptidases and Carboxypeptidases.

• Aminopeptidases: Converts kallidin to bradykinin
• Carboxypeptidase: There are two forms-
  1. Kininase I
  2. Kininase II (ACE)

Generation and degradation of plasma kinins

Pharmacological actions of kinins

Bradykinin and kallidin have similar actions-

• Cardiovascular system
  • Plasma kinins are potent vasodilators.
  • Renal, cardiac and other visceral vessels are dilated. Kinin induced vasodilatation, causes a sharp fall in systolic and diastolic pressure.
  • ACE inhibitors increase the level of kinins in tissues and plasma.
• Kidney
  • Kinins regulate urine volume and composition.
  • They increase renal blood flow and enhance the electron transport of chloride in the collecting duct.
• Other effects 
  • Kinins function in male reproductive system in areas such as spermatogenesis and in promoting sperm motility.
  • Kinins promote dilatation of the femoral artery, closure of the ductus arteriosus and constriction of umbilical vessels helping in the adjustment from foetal to neonatal circulation.

Pathophysiological role of kinins

• Mediation of inflammation
  • Kinins produce all signs of inflammation – redness, exudation, pain and leukocyte mobilization.
  • Tissue injury can cause local kinin production that sets in motion the various defensive and reparative processes.
  • In chronic inflammatory disease there is an increase in kinin level.
• Mediation of pain
  • By directly stimulating the nerve endings and by increasing the prostaglandin secretion kinins mediate pain.
• Other actions
  • Functional hyperemia in glands during secretion and regulation of microcirculation specially in kidney may be occurring through local kinin production.
  • Production of kinin is integrated with clotting, fibrinolysin and complement systems.
  • Kinins cause closure of ductus arteriosus, dilatation of foetal pulmonary artery and constriction of umbilical vessels.
  • Kinins may also be involved in shock, angioedema, rhinitis, asthma, ACE inhibitor induced cough, acute pancreatitis etc.

Clinical uses of kinins

Kinins are used in conditions of male infertility due to asthenozoospermia and oligospermia. also used in increasing the delivery of cancer chemotherapeutic agents beyond the blood brain barrier.