Cyclooxygenase inhibition and rosuvastatin-induced vascular protection in the setting of ischemia–reperfusion: A human in vivo study

• Published in: Vascular pharmacology 2015-08, Vol.71, p.159-165
• Main Authors: Kwong, Wilson, Liuni, Andrew, Zhou, Kangbin, Parker, John D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiovascular; Cyclooxygenase inhibition; Cyclooxygenase Inhibitors - administration & dosage; Drug Therapy, Combination; Endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Flow-mediated dilation; Heart Rate - drug effects; Heart Rate - physiology; Humans; Male; Non-steroidal anti-inflammatory drugs; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Rosuvastatin Calcium - administration & dosage; Single-Blind Method; Vasodilation - drug effects; Vasodilation - physiology; Young Adult
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2015.03.010

Abstract The 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitors have preconditioning effects involving up-regulation of cyclooxygenase (COX)-2. We investigated the effect of selective and non-selective COX inhibition on rosuvastatin-mediated protection against ischemia–reperfusion (IR)-induced endothelial dysfunction in the human forearm. Healthy volunteers (n = 66) were allocated to placebo, acetylsalicylic acid (ASA) 81 mg daily, ASA 325 mg daily, celecoxib 200 mg twice daily or 400 mg ibuprofen four times daily, each administered for 5 to 7 days. On the last day of study drug therapy, subjects received a single dose of 40 mg rosuvastatin. Twenty-four hours later flow-mediated dilation (FMD) of the radial artery was evaluated before and after IR. In the placebo group, FMD was similar before and after IR (8.1 ± 1.0 vs 7.2 ± 0.8%; P = NS) indicating a significant protective effect of rosuvastatin. There was also no effect of IR on FMD in the ASA 81 mg group (6.7 ± 0.6 vs 6.1 ± 0.7%; P = NS). In contrast, following IR there was a significant decrease in FMD in the ASA 325 mg group (7.2 ± 0.8 vs 3.3 ± 0.7%, P < 0.001), the celecoxib group (7.3 ± 1.5 vs 2.6 ± 1.5%, P < 0.01) as well as the ibuprofen group (6.8 ± 0.7 vs 2.6 ± 0.8%; P < 0.01). Therefore, nonselective COX inhibition with ASA 325 mg and ibuprofen completely inhibit the protective effects of rosuvastatin in the setting of IR injury, as does therapy with the specific COX-2 antagonist celecoxib. In contrast, therapy with low dose ASA (81 mg daily) does not have such inhibitory effects.