An unexpected negative inotropic effect of prostaglandin F2alpha in the rat heart.
Prostaglandin F(2alpha) (PGF(2alpha)) is produced during myocardial inflammation and many of the insults that trigger contractile dysfunction also activate prostaglandin synthesis and production. However, although PGF(2alpha) plays a significant role in the cardiac response to inflammation, the effect of this particular compound on the heart was largely studied at the cellular level and probably no due attention was paid to the effect of PGF(2alpha) on the whole heart contractility. Therefore, in the present study we have investigated the effect of PGF(2alpha) on isolated right ventricle of the rat heart. PGF(2alpha) (1nM-1microM) induced concentration-dependent decrease of the amplitude of contractions of the ventricular muscle. Real time RT-PCR has revealed that prostaglandin FP receptors are expressed in the rat myocardium and the level of expression was similar to those of creatine kinase and adenylate kinase, which are proteins abundantly present in the heart. An antagonist of FP receptors, PGF(2alpha) dimetilamide (10nM), abolished negative inotropic effect induced by PGF(2alpha). To examine the possibility that PGF(2alpha) could activate non-FP prostaglandin receptor, we have measured the level of expression of all known prostaglandin receptors in the rat heart. These experiments have shown that the order of expression of prostaglandin receptors in the rat heart is FP>>EP1=TP>EP4>EP3>DP=IP. Based on the obtained results we conclude that PGF(2alpha) induces negative inotropic effect on rat heart by activating FP prostaglandin receptors. This effect of PGF(2alpha) could contribute to cardiac dysfunction in conditions of systemic and myocardial inflammation.
Jovanović
Nenad
N
Division of Experimental Pharmacology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia. a.jovanovic@dundee.ac.uk
Pavlović
Mirjana
M
Mircevski
Vladimir
V
Du
Qingyou
Q
Jovanović
Aleksandar
A
D000818:Animals; D003864:Depression, Chemical; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; C032516:prostaglandin F2alpha N-dimethylamide; D015237:Dinoprost