Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of guinea-pigs: Role of glycoprotein IIB/IIIA receptors

• Published in: Cardiovascular research Vol. 57; no. 1; pp. 109 - 118
• Main Authors: MOLERO, Laura, FARRE, Jeronimo, GARCIA-MENDEZ, Antonio, JIMENEZ MATEOS-CACERES, Petra, CARRASCO MARTIN, Carolina, MILLAS, Inmaculada, NAVARRO, Felipe, CORDOBA, Manuel, CASADO, Santos, LOPEZ-FARRE, Antonio
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 2003
• Subjects: Animals; Biological and medical sciences; Blood Platelets - metabolism; Cells, Cultured; Cyclooxygenase 2; Endothelin-1 - pharmacology; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Heart; Isoenzymes - analysis; Isoenzymes - metabolism; Leukocytes, Mononuclear - metabolism; Male; Myocardium - metabolism; Platelet Count; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Prostaglandin-Endoperoxide Synthases - analysis; Prostaglandin-Endoperoxide Synthases - metabolism; Stimulation, Chemical; Thromboplastin - analysis; Thromboplastin - metabolism; Tirofiban; Tyrosine - analogs & derivatives; Tyrosine - pharmacology; Vertebrates: cardiovascular system; Heart; Pharmacologic test; Prostaglandin-endoperoxide synthase; Endothelins; Leukocyte; Endothelial factors; Peptide hormone; Tissue factor; Leukocytes; Myocytes; Guinea pig; Vasoconstrictor agent; Biological receptor; Glycoprotein IIbIIIa; Enzyme; Rodentia; Exploration; Endothelin 1; Gene expression; Biological activity; Vertebrata; Platelet; Mammalia; Infection/inflammation; Animal; Myocardium; Circulatory system; Oxidoreductases; Platelets
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(02)00657-0

To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed.
ET-1 (0.013 microg/min) was infused to male guinea-pigs for 45 min in the presence and absence of tirofiban, a nonpeptidic blocker of the glycoprotein IIb/IIIa receptor (GPIIb/IIIa). Tissue factor and COX-2 expression were determined by Western blot.
No changes in mean arterial pressure and heart rate were detected. ET-1-infused guinea-pigs showed a marked increase in the number of platelets expressing activated GPIIb/IIIa receptors (0.8+/-0.03% vs. 6.5+/-0.2%; P<0.05). Tirofiban (10 microg/Kg bw/min) blunted ex vivo platelet aggregation in response to ADP, although only partially reduced COX-2 and tissue factor expression in both the myocardium and leukocytes of ET-1-infused guinea-pigs. The myocardium of platelet-depleted guinea-pigs also showed a reduced COX-2 expression after ET-1 infusion (57+/-3% reduction; P<0.05). In vitro studies demonstrated that platelets (10(7) and 10(9) platelets/well) enhanced ET-1 (10(-7) mol/l)-induced COX-2 expression in heart slices.
ET-1 stimulated in vivo the expression of the pro-inflammatory proteins COX-2 and tissue factor in the myocardium and in leukocytes by a mechanism GPIIb/IIIa platelet receptors.