Endothelin 1 mediates ex vivo coronary vasoconstriction caused by exogenous and endogenous cytokines. 1995

P Klemm, and T D Warner, and T Hohlfeld, and R Corder, and J R Vane
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.

Treatment of rats with cytokines has been associated with an increase in the circulating levels of endothelin 1 (ET-1). Here we show that administration of tumor necrosis factor alpha (TNF-alpha; 4 micrograms.kg-1) to anesthetized rats caused within 15 min a strong elevation in the circulating levels of ET-1. This was associated with a striking coronary vasoconstriction in hearts from these animals when they were removed and perfused in vitro by the Langendorff technique. This vasoconstriction was largely overcome by treatment with either the endothelin type A (ETA) receptor antagonist FR 139317 or antibody against ET-1. Furthermore, it was mimicked by in vivo exposure to exogenous ET-1. Endogenously produced TNF-alpha may also cause such a coronary vasoconstriction, for treatment with interleukin 2 (600 micrograms.kg-1) produced an increase in coronary perfusion pressure that correlated with the increases in circulating TNF-alpha. This coronary vasoconstriction was substantially reversed by treatment either with antibody against TNF-alpha or with FR 139317. We suggest, therefore, that cytokine-driven changes in the production of ET-1 are key events in the development of vascular pathologies.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

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