Involvement of platelet activating factor in immediate heart response to lipopolysaccharide

• Autorzy: Jakubowski A. , Olszanecki R. , Chlopicki S.
• Języki publikacji: EN

Abstrakty

EN

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, TXA2 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 min-1 and 560 ± 81 mmHg 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 TXA2 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.

Słowa kluczowe

EN

platelet-activating factor; lipopolysaccharide; cardiovascular response; heart; endotoxic shock; rat

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2004
• Tom: 55
• Numer: 2
• Opis fizyczny: p.409-421,fig.,ref.

Twórcy

autor

Jakubowski A.

• Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Krakow, Poland

autor

Olszanecki R.

autor

Chlopicki S.