Premium
Resveratrol attenuates endothelium‐dependent cyclooxygenase‐mediated contractile activity in the carotid artery of spontaneously hypertensive rats (855.6)
Author(s) -
Rush James,
Denniss Steven,
Smith Christopher,
Jeffery Andrew,
Ford Rebecca
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.855.6
Subject(s) - contraction (grammar) , acetylcholine , medicine , endocrinology , cyclooxygenase , endothelium , prostaglandin , spontaneously hypertensive rat , blood pressure , chemistry , enzyme , biochemistry
The objective of this study was to determine the chronic and acute effects of resveratrol (RSV) on endothelial function and endothelium‐derived contracting factor (EDCF) signaling using common carotid artery (CCA) isolated from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)‐stimulated endothelium‐dependent relaxation in pre‐contracted CCA was impaired in SHR (max. 53±6% vs. 86±6% in WKY) caused by competitive cyclooxygenase (COX)‐mediated contraction at high [Ach]. Chronic (28‐day) treatment in vivo (via drinking water) with a moderate RSV dose (Mod‐RSV, ~0.075 mg/kg/day) was without effect on Ach‐stimulated relaxation, or Ach‐stimulated contraction and associated prostaglandin (PG) production in quiescent CCA, in either strain. In contrast, in SHR but not WKY, a chronic high RSV dose (High‐RSV, ~7.5 mg/kg/day) improved Ach‐stimulated relaxation (max. 99±5% vs. 53±6% in No‐RSV SHR), and attenuated Ach‐stimulated contraction (55±5% vs. 68±5% in No‐RSV SHR) and associated PG production (189±30 vs. 519±93 pg/ml in No‐RSV SHR) (all p<0.05). High‐RSV also reduced mean arterial pressure in SHR (159±6 vs. 176±6 mmHg in No‐RSV SHR; p<0.05). In separate experiments, acute (30 min) in vitro treatment (in‐bath pre‐incubation) with 20µM RSV (RSV‐20µM) nearly abolished Ach‐stimulated contraction and greatly attenuated the associated PG production in SHR and WKY CCA (all p<0.05). Taken altogether, these experiments demonstrate that RSV can reverse endothelial dysfunction caused by EDCF activity by a signaling mechanism predominately involving the attenuation of COX‐derived PG production. Grant Funding Source : Supported by NSERC Canada RGPIN 238342