Cyclooxygenase Involvement in Thromboxane-Dependent Contraction in Rat Mesenteric Resistance Arteries
Autor: | Sylviane Levy-Toledano, Bernard I. Levy, Laurent Loufrani, Manlio Bolla, Aida Habib, Dong You, Daniel Henrion |
---|---|
Rok vydání: | 2004 |
Předmět: |
Male
Contraction (grammar) Thromboxane Indomethacin 030204 cardiovascular system & hematology Dinoprost Rats Inbred WKY Receptors Thromboxane A2 Prostaglandin H2 Thromboxane A2 chemistry.chemical_compound 0302 clinical medicine Organic Chemicals Mesenteric arteries Sulfonamides 0303 health sciences Endothelin-1 biology Chemistry Anti-Inflammatory Agents Non-Steroidal Mesenteric Arteries Isoenzymes Hydrazines medicine.anatomical_structure Fatty Acids Unsaturated lipids (amino acids peptides and proteins) medicine.symptom medicine.medical_specialty Dinoprostone Article Cyclooxygenase pathway 03 medical and health sciences Internal medicine Internal Medicine medicine Animals Cyclooxygenase Inhibitors 030304 developmental biology Aspirin Cyclooxygenase 2 Inhibitors Membrane Proteins Bridged Bicyclo Compounds Heterocyclic Rats Endocrinology Flurbiprofen Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Vasoconstriction 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Cyclooxygenase 1 biology.protein Pyrazoles Vascular Resistance Cyclooxygenase Thromboxane-A synthase |
Zdroj: | Hypertension. 43:1264-1269 |
ISSN: | 1524-4563 0194-911X |
Popis: | The influence of cyclooxygenase pathway activation following thromboxane-endoperoxide (TP) receptor stimulation was studied in rat mesenteric resistance arteries (n=6 to 10 per group). We studied isolated, perfused, and pressurized mesenteric resistance arteries (mean internal diameter 214 μm) using an arteriograph, enabling us to study arteries in physiological conditions of flow and pressure. Changes in diameter were continuously recorded, and contractions measured as internal diameter reduction. Release of cyclooxygenase pathway metabolites was also assessed by enzyme immunoassay (EIA) analysis of mesenteric bed perfusions. The thromboxane A2 (TxA 2 ) analog U-46619 (1 μmol/L) induced a significant contraction (108 μm maximal diameter reduction). Inhibition by 3 chemically different cyclooxygenase inhibitors (ie, flurbiprofen, indomethacin, and aspirin) potently reduced the contraction to 27%, 25%, and 6% of control, respectively. The selective cyclooxygenase-1 inhibitor SC-58560 inhibited U-46619 contraction, whereas selective cyclooxygenase-2 inhibition (SC-58236) had no effect. Thromboxane synthase inhibition (furegrelate) did not affect U-46619-induced contraction, but it was reduced by cytosolic phospholipase A2 inhibition. Measurement of cyclooxygenase derivatives produced by the isolated mesenteric bed showed that PGE 2 was produced after TxA 2 -receptor stimulation with U-46619. Exogenous prostaglandin E 2 (in the presence of the TxA 2 receptor antagonist SQ 29 548) and U-46619 contracted mesenteric arteries with a similar potency (EC 50 : 0.30 and 0.48 μmol/L, respectively). This study provides the first evidence that TxA 2 -receptor-dependent contraction in a resistant artery involved cyclooxygenase stimulation and, at least in part, a PGE 2 formation. This mechanism of TxA 2 -dependent contraction in resistant arteries might be of importance in the understanding of diseases affecting resistant arteries and involving TxA 2 , such as hypertension. |
Databáze: | OpenAIRE |
Externí odkaz: |