Pericardial fluid of cardiac patients elicits arterial constriction: role of endothelin-1

• Published in: Canadian journal of physiology and pharmacology 2015-09, Vol.93 (9), p.779-785
• Main Authors: Nemeth, Zoltan, Cziraki, Attila, Szabados, Sandor, Horvath, Ivan, Koller, Akos
• Format: Article
• Language: English
• Subjects: Animals; Arteries; Body fluids; Cardiac patients; Cardiovascular disease; Carotid Arteries - physiology; Coronary Artery Disease - surgery; Endothelin; Endothelin Receptor Antagonists - pharmacology; Endothelin-1 - analysis; Endothelin-1 - physiology; Health aspects; Humans; In Vitro Techniques; Male; Peptides, Cyclic - pharmacology; Pericardial Fluid - chemistry; Pericardial Fluid - physiology; Pericardium; Physiological aspects; Potassium Chloride - pharmacology; Proteins; Rats; Vasoconstriction - drug effects; Vasoconstriction - physiology; Veins & arteries
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2015-0030

Recently, several vasoactive molecules have been found in pericardial fluid (PF). Thus, we hypothesized that in coronary artery disease due to ischemia or ischemia-reperfusion, the level of vasoconstrictors, mainly endothelin-1 (ET-1), increases in PF, which can increase the vasomotor tone of arteries. Experiments were performed using an isometric myograph. Vasomotor effects of PF from patients undergoing coronary artery bypass graft (PFCABG, n = 14) or valve replacement (PFVR, n = 7) surgery were examined in isolated rat carotid arteries (N = 14; n = 26). Vasomotor responses to KCl (40 or 60 mmol/L) were also tested. The selective endothelin A receptor antagonist BQ123 (10(-6) mol/L) was used to elucidate the role of ET-1. Both the first and the second additions of KCl elicited increases in the isometric force of the isolated arteries (KCl1, 6.1 ± 0.2 mN; KCl2, 6.5 ± 0.9 mN). PFCABG and PFVR elicited substantial increases in the isometric force of arteries (PFCABG, 3.1 ± 0.7 mN; PFVR, 3.0 ± 0.9 mN; p > 0.05). The presence of the selective endothelin A receptor blocker significantly reduced arterial contractions to PFCABG (before BQ123, 2.6 ± 0.5 mN vs. after BQ123, 0.8 ± 0.1 mN; p < 0.05). This study is the first to demonstrate that PFs of patients elicit substantial arterial constrictions, which is mediated primarily by ET-1. Interfering with the vasoconstrictor action of PF could be a potential therapeutic target to improve coronary blood flow in cardiac patients.