Nursing Pharmacology Chapter 24: Vasoactive Peptides
Kinins: potent vasodilator peptides
Kinins formed from kininogens, catalyzed by kallikreins (or kininogenases)
Kallikreins-kinin: similar to renin angiotensin system in certain respects
Plasma
Tissues: kidneys, pancreas, intestine, salivary glands, sweat glands
Serine proteases (catalytically similar to trypsin, chymotrypsin, thrombin, elastase, plasmin)
Prekallikrein produced by the liver
Kallikreins in some glands exist as Prekallikreins
Prekallikrein is conveted to kallikrein
Conversion catalyzed by: trypsin, Hageman factor, kallikrein itself (possibly)
Kininogens --precursors of kinins; kallikreins substrate
Plasma
Low molecular weight (LMW)kininogen
High molecular weight (HMW) kininogen
HMW form (15-20% of total plasma kininogen) remains in the blood: substrate for plasma kallikrein
LMW form: crosses capillary walls -- substrate for tissue kallikreins
Lymph
Interstitial fluid
Tissue and plasma Kinin formation:
Three kinins:
Bradykinin
Lysylbradykinin
Methionyllysylbradykinin
Bradykinin: released by plasma kallikreinin
Lysylbradykinin: released by glandular kallikrein
Methionyllysylbradykinin: released by pepsins and pepsin-like enzymes
Preferred substrate for plasma kallikrein:
HMW kininogen
Preferred substrate for tissue kallikrein:
LMW kininogen
Bradykinin: major plasma kinin
Lysylbradykinin: major urinary kinin
Methionyllysylbradykinin: found in acid urine (acid activates uropepsinogen, catalyzing release of methionyllysylbradykinin from urinary kininogens
Kinins: Physiological Effects:
Vasodilation: vascular beds:
Heart
Kidney
Intestine
Skeletal muscle
Lver
Mechanism of Action (possible): vasodilation
Drect effect of kinins on arteriolar, vascular smooth muscle
Mediated by nitric oxide (EDRF)
Mediated by vasodilator prostaglandins (PGE2 and PGI2)
Vasoconstriction: vascular beds
Venous smooth muscle
Mechanism of Action: vasoconstriction
Direct venous smooth muscle stimulation
Release of venoconstrictor prostaglandins (PGF2-a )
Visceral smooth muscle
Hypotensive response (brief)
Reflex tachycardia, positive inotropism: increased cardiac output compensates
Arteriolar dilation: Mechanism of Action --
Increase in capillary bed pressure and flow
Promotes fluid transfer from blood to tissue (increased capillary permeability may occur because of endothelial cell contraction which widens intercellular junctions)
Increased venous pressure (following venous constriction) also promotes fluid transfer to tissue.
Edema may result
Endocrine and Exocrine Gland Effects:
Prekallikreins and kallikreins present in:
Kidney
Pancreas
Intestine
Salivary glands
Sweat glands
Enzymes or kinins may diffuse from organs to blood, acting as local regulators of blood flow
Kinins may (because of smooth muscle effects) influence salivary and pancreatic ducts tone; and may influence gastrointestinal motility
Kinins affect transepithelial transport of:
Water
Electrolytes
Amino acids
Glucose
Kallikreins may be involved in physiological activation of prohormones, i.e. proinsulin and prorenin
Kallikreins and kinins: produce inflammatory symptoms
Potent pain-producing (intradermal application)
Mechanism of Action: stimulation of nociceptive afferents.
Reid, I.A., Vasoactive Peptides, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 287-303.