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

BACKGROUND AND AIMS: Proton 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 METHODS: Isolated 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 FINDINGS: Vascular 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 ±â€¯1.42%, 10 µM: 34.64 ±â€¯0.90% and 100 µM: 31.50 ±â€¯0.67% vs. control 74.39 ±â€¯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 ±â€¯2.50%) compared with the control group (72.47 ±â€¯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 ±â€¯3.52 s vs. 15.30 ±â€¯0.70 s, p < 0.05; aPTT 96.1 ±â€¯4.62 s vs. 48 ±â€¯1.97 s, p < 0.05, respectively). SIGNIFICANCE: The 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.