Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II
Figure 1
RWPs treatment prevents the doxorubicin-induced blunted EDH-mediated relaxations in the rat mesenteric artery. Twelve-week-old male Wistar rats were assigned into 4 groups: the control group receiving the doxorubicin vehicle (DMSO, IP) and the RWPs-solvent (ethanol 3% V/V, per os); the RWPs group receiving the doxorubicin vehicle and RWPs (75 mg/kg/day, per os); the doxo group receiving doxorubicin (2.5 mg/kg/week, IP) for 3 subsequent weeks starting at the age of 12 weeks followed again by injections (2.5 mg/kg/week) for 3 subsequent weeks starting at the age of 28 weeks, with the RWPs solvent per os; the doxorubicin + RWPs group receiving doxorubicin and RWPs. Mesenteric artery rings with endothelium from the indicated groups of rats were contracted with phenylephrine in the presence of indomethacin (10 μM) to inhibit the formation of prostanoids, in the presence of (a) charybdotoxin (100 nM) plus apamin (100 nM) to inhibit the participation of EDH, in the presence of (b) Nω-nitro-L-arginine (L-NA, 300 μM) to rule out the formation of NO before a concentration-relaxation curve to ACh was constructed. Concentration-relaxation curves to sodium nitroprusside (SNP, (c)) and levcromakalim (LEV, (d)) in mesenteric artery rings without endothelium are demonstrated. Results are shown as mean ± SEM of 5 to 6 different rats. indicates a significant difference versus control rats, and versus doxorubicin-treated rats.
