Mechanism of the positive inotropic effect of lysophosphatidic acid in rat heart.
BACKGROUND
Lysophosphatidic acid, a bioactive phospholipid, is mainly released from the activated platelets. The concentration of lysophosphatidic acid in serum is elevated under conditions such as ischemia, hypertension, and thrombosis; however, its effect on cardiac function, as well as the mechanisms of its action, have not been fully understood.


RESULTS
Cardiovascular effects of lysophosphatidic acid were studied in vivo in rats as well as in vitro by using the isolated perfused heart and cardiomyocyte preparations. Intravenous injection of lysophosphatidic acid (2.8 to 14 microg/100 g body wt) increased the left ventricular systolic and diastolic pressures, rate of pressure development, and rate of pressure decay in rats. The positive inotropic effect of lysophosphatidic acid in vivo was not affected by the blockers of angiotensin II, endothelin-1, or adrenergic receptors, but this action was abolished by pretreatment with neurokinin type 1 receptor antagonist (L703606) as well as Ca2+-channel antagonist (verapamil). In the isolated heart, lysophosphatidic acid (1-10 microM) had no significant effect on cardiac function but higher concentrations (20-50 microM) elevated the left ventricular end diastolic pressure, significantly. Lysophosphatidic acid (1-30 microM) neither showed any effect on the basal intracellular concentration of free Ca2+ nor modified the KCl-induced increase in [Ca2+]i in freshly isolated cardiomyocytes.


CONCLUSIONS
These results indicate that lysophosphatidic acid stimulated heart function under in vivo but not in vitro conditions. The positive inotropic effect of lysophosphatidic acid in vivo may be indirectly mediated by the activation of neurokinin type 1 receptors.
Xu
Yan-Jun
YJ
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Manitoba, Winnipeg, Canada.
Rathi
Satyajeet S
SS
Zhang
Ming
M
Bhugra
Praveen
P
Dhalla
Naranjan S
NS
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018663:Adrenergic Agents; D002317:Cardiovascular Agents; D008246:Lysophospholipids; D002118:Calcium