52 - Ranitidine treatment impairs vascular redox biology and function

Abstract

Proton pump inhibitors (PPIs) are considered safe drugs. However, recent studies suggest that omeprazole adversely affects vascular function, impairs vascular redox biology and promotes endothelial dysfunction. These findings are relevant to patients with cardiovascular diseases using PPIs, and therefore investigating whether other drugs used to treat dyspeptic diseases cause similar problems is important. In this context, the impact of ranitidine on vascular biology and function remains unknown. We examined the effects of ranitidine on blood pressure, vascular function and redox biology. Male Wistar rats (180-200 g) were treated once daily for four weeks with vehicle (V) or ranitidine (R) 100 mg/kg orally. Omeprazole (O) 10 mg/kg i.p. was used as a positive control. Systolic blood pressure (SBP) was assessed weekly by tail-cuff plethysmography. By the end of the fourth week of treatment, the animals were euthanized and the gastric washing pH was evaluated. Endothelial integrity was examined by assessing the relaxation in response to acetylcholine. To assess vascular oxidative stress, two independent biochemical assays were used: dihydroethidium (DHE) and chemiluminescent lucigenin assay. Results Ranitidine or omeprazole did not affect SBP. Gastric pH increased with both treatments. Ranitidine or omeprazole decreased the maximum responses of aortic rings in response to acetylcholine (Emax: V=106.5±2.0%; O=92.2±2.1%; R=93.9±1.7%; both P Conclusion Ranitidine and omeprazole have similar pro-oxidant effects on the vasculature and cause endothelial dysfunction.