Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery
| Autor: | Andrew J. Jeffery, Rebecca J Ford, Steven G Denniss, James W. E. Rush, Christopher Smith |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Contraction (grammar) Physiology Receptors Thromboxane Vasodilation AMP-Activated Protein Kinases 030204 cardiovascular system & hematology Rats Inbred WKY chemistry.chemical_compound 0302 clinical medicine Rats Inbred SHR Stilbenes Vasoconstrictor Agents biology food and beverages Articles Nitric oxide synthase Hypertension cardiovascular system medicine.symptom Muscle Contraction Signal Transduction Muscle contraction medicine.medical_specialty Nitric Oxide Synthase Type III Carotid Artery Common Prostaglandin 03 medical and health sciences Physiology (medical) Internal medicine medicine Animals business.industry fungi AMPK Acetylcholine Rats 030104 developmental biology Endocrinology chemistry Prostaglandin-Endoperoxide Synthases Resveratrol Vasoconstriction 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Prostaglandins biology.protein Endothelium Vascular Cyclooxygenase business |
| Zdroj: | Journal of Applied Physiology. 120:1141-1150 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00675.2015 |
| Popis: | Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) ( P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg−1·day−1 RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg−1·day−1 RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619 -stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by AMPK. |
| Databáze: | OpenAIRE |
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