Pantoprazole reduces vascular relaxation in-vitro and ex-vivo and interferes with blood coagulation in an animal model

Abstract

Background and aimsProton pump inhibitors (PPIs) are effective antagonists of gastric acid secretion used to treat a number of gastro-esophageal disorders. The present study investigated the effect of Pantoprazole on vascular relaxation in-vitro and ex-vivo and its effect on blood coagulation in an animal model. Main methodsIsolated mouse arterial rings were pre-contracted in-vitro with phenylephrine and concentration–response curves to the acetylcholine relaxing effect were constructed in the presence of escalating concentrations of pantoprazole. In another set of experiments, male albino mice weighing ∼25 g were administered a daily dose of pantoprazole (0.4 mg by oral gavage) for four consecutive weeks; a vehicle control group was run in parallel. At the end of the treatment period, thoracic aorta was isolated for the assessment of vascular function ex-vivo. Blood samples were also collected to evaluate the effect of chronic pantoprazole therapy on coagulation parameters, namely, prothrombin time (PT) and activated partial thromboplastin time (aPTT). Key findingsVascular responsiveness to acetylcholine demonstrated a reduced relaxation of the arterial ring from baseline in the presence of different concentrations of pantoprazole (1 μM: 54.69 ± 1.42%, 10 μM: 34.64 ± 0.90% and 100 μM: 31.50 ± 0.67% vs. control 74.39 ± 1.426%, p < 0.001). Furthermore, acetylcholine-induced relaxation of the aorta was significantly diminished after four weeks of administrating pantoprazole to mice (37.12 ± 2.50%) compared with the control group (72.47 ± 1.68%, p < 0.001). This, however, wasn’t accompanied by significant changes in the phenylephrine-induced vasoconstriction. Animals that received pantoprazole daily for four weeks also exhibited increased blood coagulation time in comparison to the vehicle control group (PT 45.30 ± 3.52 s vs. 15.30 ± 0.70 s, p < 0.05; aPTT 96.1 ± 4.62 s vs. 48 ± 1.97 s, p < 0.05, respectively). SignificanceThe results of the present investigation suggest that pantoprazole reduces arterial relaxation and interferes with blood coagulation. Additional studies are warranted to assess the clinical implications of such observations.