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Involvement of platelet activating factor in immediate heart response to lipopolysaccharide.
J Physiol Pharmacol. 2004 Jun; 55(2):409-21.JP

Abstract

Although lipopolysaccharide (LPS) is recognized to induce a biphasic cardiovascular response its mechanism is not fully elucidated. In this study we analysed the involvement of PAF, TXA(2) and cysteinyl leukotrienes (cysLTs) in the acute cardiovascular effects of LPS in the isolated rat heart as well as in delayed phase of LPS response using a surrogate cellular model of the induction of NOS-2 by LPS in mouse macrophages. Perfusion of rat hearts with LPS resulted, in an immediate fall in heart contractility and coronary flow by 2.5 +/- 0.59 ml x min(-1) and 560 +/- 81 mmHg x sec(-1), respectively. This response was fully blocked by platelet activating factor (PAF) antagonist - WEB 2170 and partially inhibited, by inhibitor of cyclooxygenase (indomethacin) or by inhibitor of thromboxane synthase (camonagrel). The inhibition of leukotriene synthesis (BAY x1005) or cysLTs receptors (BAY x7195) was without effect. Administration of stable PAF analog (methylcarbamyl-PAF - MC-PAF) alone, mimicked heart response to LPS. In cultured mouse macrophages, MC-PAF did not induce NOS-2 expression and when given with LPS it slightly potentiated NOS-2 induction by LPS. However, in presence of WEB 2170 NOS-2 induction by LPS was inhibited in a dose-dependent manner. Inhibition of cyclooxygenase and leukotriene pathways had no effect on NOS-2 induced by LPS. These results indicate that PAF and TXA(2) but not cysLTs mediate the instant heart response induced by LPS, while PAF alone mediates a delayed NOS-2 induction by LPS. Accordingly, PAF may constitute the mediator that links acute and delayed phases of LPS-induced cardiovascular response.

Authors+Show Affiliations

Department of Experimental Pharmacology, Jagiellonian University Medical College, Cracow, Poland.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15213362

Citation

Jakubowski, A, et al. "Involvement of Platelet Activating Factor in Immediate Heart Response to Lipopolysaccharide." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 55, no. 2, 2004, pp. 409-21.
Jakubowski A, Olszanecki R, Chlopicki S. Involvement of platelet activating factor in immediate heart response to lipopolysaccharide. J Physiol Pharmacol. 2004;55(2):409-21.
Jakubowski, A., Olszanecki, R., & Chlopicki, S. (2004). Involvement of platelet activating factor in immediate heart response to lipopolysaccharide. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 55(2), 409-21.
Jakubowski A, Olszanecki R, Chlopicki S. Involvement of Platelet Activating Factor in Immediate Heart Response to Lipopolysaccharide. J Physiol Pharmacol. 2004;55(2):409-21. PubMed PMID: 15213362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of platelet activating factor in immediate heart response to lipopolysaccharide. AU - Jakubowski,A, AU - Olszanecki,R, AU - Chlopicki,S, PY - 2003/07/31/received PY - 2004/03/18/accepted PY - 2004/6/24/pubmed PY - 2004/12/23/medline PY - 2004/6/24/entrez SP - 409 EP - 21 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J Physiol Pharmacol VL - 55 IS - 2 N2 - Although lipopolysaccharide (LPS) is recognized to induce a biphasic cardiovascular response its mechanism is not fully elucidated. In this study we analysed the involvement of PAF, TXA(2) and cysteinyl leukotrienes (cysLTs) in the acute cardiovascular effects of LPS in the isolated rat heart as well as in delayed phase of LPS response using a surrogate cellular model of the induction of NOS-2 by LPS in mouse macrophages. Perfusion of rat hearts with LPS resulted, in an immediate fall in heart contractility and coronary flow by 2.5 +/- 0.59 ml x min(-1) and 560 +/- 81 mmHg x sec(-1), respectively. This response was fully blocked by platelet activating factor (PAF) antagonist - WEB 2170 and partially inhibited, by inhibitor of cyclooxygenase (indomethacin) or by inhibitor of thromboxane synthase (camonagrel). The inhibition of leukotriene synthesis (BAY x1005) or cysLTs receptors (BAY x7195) was without effect. Administration of stable PAF analog (methylcarbamyl-PAF - MC-PAF) alone, mimicked heart response to LPS. In cultured mouse macrophages, MC-PAF did not induce NOS-2 expression and when given with LPS it slightly potentiated NOS-2 induction by LPS. However, in presence of WEB 2170 NOS-2 induction by LPS was inhibited in a dose-dependent manner. Inhibition of cyclooxygenase and leukotriene pathways had no effect on NOS-2 induced by LPS. These results indicate that PAF and TXA(2) but not cysLTs mediate the instant heart response induced by LPS, while PAF alone mediates a delayed NOS-2 induction by LPS. Accordingly, PAF may constitute the mediator that links acute and delayed phases of LPS-induced cardiovascular response. SN - 0867-5910 UR - https://www.unboundmedicine.com/medline/citation/15213362/Involvement_of_platelet_activating_factor_in_immediate_heart_response_to_lipopolysaccharide_ L2 - http://www.jpp.krakow.pl/journal/archive/06_04/pdf/409_06_04_article.pdf DB - PRIME DP - Unbound Medicine ER -