Page 306 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Eicosanoids
Eicosanoids are a large group of intracellular hormones and the contraction of the smooth
and intercellular mediators that are formed muscles of blood vessels, gut, bronchi, and
from arachidonic acid, a polyunsaturated fatty uterus.
acid. They are rapidly inactivated in the blood PGE 2 inhibits the release of hormones and
and thus act mainly on their immediate envi- lipolysis, stimulates the contraction of smooth
ronment. muscles of the gut and uterus; however, it in-
Arachidonic acid is released from phospho- hibits the contraction of the vascular and bron-
lipids of the cell membrane under the influ- chial muscles. Cyclo-oxygenase inhibitors can
ence of the enzyme phospholipase A 2 (→ A1). thus cause asthma in an atopic individual (so-
This enzyme is activated by cell swelling and called analgesic asthma). The vascular effect
by an increase of intracellular Ca 2+ concentra- can cause persistence of the ductus arteriosus.
tion. It is stimulated by a number of mediators, Conversely, the administration of cyclo-oxy-
such as histamine, serotonin, bradykinin, and genase inhibitors during the last trimester can
norepinephrine (via α-receptors). Phopholi- cause the premature closure of the ductus ar-
pase A 2 is inhibited by glucocorticoids (via li- teriosus. PGE 2 increases glomerular filtration
pocortin) and epinephrine (via β-receptors). rate. It raises vascular permeability and thus
Hormones kotrienes via the enzyme lipoxygenase and to the bones (osteolysis). They stimulate the re-
promotes the development of edemas.
Arachidonic acid can be transformed to leu-
PGE 2 and PGI 2 aid in the demineralization of
prostacyclin (prostglandin G [PGG 2 ]) via the
+
tubular reabsorption of Na and water, they
9 enzyme cyclo-oxygenase. Substances that can nal formation of renin and, by inhibiting the
be formed from PGG 2 include thromboxan A 2
produce natriuresis and diuresis. They raise
(TXA 2 ) and the prostaglandins F 2α (PGF 2α ), E 2
(PGE 2 ), and I 2 (PGI 2 = prostacyclin) (→ A3). the target level of temperature regulation (fe-
The enzyme cyclo-oxygenase is inhibited by ver) and cause pain. The effects of the prosta-
non-steroidal anti-inflammatory drugs glandins contribute to a large extent to the
(NSAIDs), for example, acetylsalicylic acid (as- symptoms of infection.
pirin). Inflammations and tissue damage cause PGE 2 has an essential, protective role in the
activation of both cyclo-oxygenase and lipoxy- stomach by inhibiting the secretion of HCl and
genase, and thus increase the formation of ei- pepsin while promoting the secretion of HCO 3 –
cosanoids. and mucus, which has a protective effect. It
The leukotrienes (→ A2) cause the contrac- also causes vascular dilation. A reduction in
tion of the smooth muscles in the bronchi, PGE 2 formation by cyclo-ogygenase inhibitors
blood vessels, gut, and uterus. They are re- favors the development of gastric ulcers.
sponsible for lasting bronchoconstriction in PGE 2 also has a protective effect on the renal
asthma; their action on the gut can cause diar- medulla. Via dilation of the vasa recta it im-
rhea and their effects on the uterus can bring proves O 2 and substrate availability, and de-
about abortion of the fetus. Leukotrienes indi- creases the expenditure of energy by inhibit-
rectly increase vascular permeability and thus ing NaCl reabsorption.
bring about edemas. They also promote adhe- PGE 2 is also of great importance in Bartter’s
sions and chemotaxis and stimulate the release syndrome, which is due to mutations of the
+
+
of histamine, oxygen radicals, and lysosomal Na -K -2 Cl – cotransporter, the luminal K +
enzymes as well as of insulin. channels, or the basolateral Cl – channels in
TXA 2 is formed largely in thrombocytes and the loop of Henle. An excessive local formation
is essential for blood clotting. An excess of of PGE 2 is the consequence of the resulting
TXA 2 favors the formation of thrombi. Admin- transport defect. The inhibitory action of PGE 2
+
istration of small doses of the cyclo-oxygenase on Na transport in more distal nephron seg-
inhibitor acetylsalicylic acid can thus reduce ments adds to NaCl loss and its vasodilator ac-
the risk of myocardial infarction because of its tion causes a profound drop in blood pressure.
296 effect of reducing thrombocyte aggregation. The affected children can be kept alive only
PGF 2α stimulates the release of a series of with inhibitors of cyclo-oxygenase.
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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