Korean J Physiol Pharmacol.
1998 Jun;2(3):331-343.
Cardioprotective effects of low dose bacterial lipopolysaccharide may
not be directly associated with prostacyclin production
- Affiliations
-
- 1Department of Physiology, Scool of Medicine, Ajou University, Suwon 442-749, Korea.
Abstract
-
Sublethal dose of bacterial lipopolysaccharide (LPS) would induce
protection against cardiac ischemic/ reperfusion (I/R) injury. This
study examines the following areas: 1) the temporal induction of the
cardioprotection produced by LPS; and 2) the relations between a degree
of protection and the myocardial prostacyclin (PGI2) production. Rats
were administered LPS (2 mg/kg, i.v.), and hearts were removed 1, 4, 8,
14, 24, 48, 72, and 96 h later. Using Langendorff apparatus,
haemodynamic differences during 25 min of global ischemia/30 min
reperfusion were investigated. The concentration of PGI2 in aliquots of
the coronary effluent was determined by radioimmunoassay as its stable
hydrolysis product 6-keto-PGF1alpha and lactate dehydrogenase release
were measured as an indicative of cellular injury. LPS-induced cardiac
protection against I/R injury appeared 4 h after LPS treatment and
remained until 96 h after treatment. PGI2 release increased 2-3 fold at
the beginning of reperfusion compared to basal level except in hearts
treated with LPS for 48 and 72 h. In hearts removed 48 and 72 h after
LPS treatment, basal PGI2 Was increased. To determine the enzymatic
step in relation to LPS-induced basal PGI2 production, we examined
prostaglandin H synthase (PGHS) protein expression, a rate limiting
enzyme of prostaglandin production, by using Western blot analysis. LPS
increased PGHS protein expression in hearts at 24, 48, 72, 96 h after
LPS treatment. Induction of PGHS expression appeared in both isotypes
of PGHS, a constitutive PGHS-1 and an inducible PGHS-2. To identify the
correlationship between PGI2 production and the cardioprotective effect
against I/R injury, indomethacin was administered in vivo or in vitro.
Indomethacin did not inhibit LPS-induced cardioprotection, which was
not affected by the duration of LPS treatment. Taken together, our
results
suggest that PGI2 might not be the major endogenous mediator of
LPS-induced cardioprotection.