Cardiovascular and biochemical studies on the effects of thrombin and dabigatran and the interaction with vasopressor molecules.

ABSTRACT

Background: The effect of serine protease thrombin and its directly acting inhibitor dabigatran were evaluated on the heart rate, blood pressure, and phospholipase C (PLC) enzyme activity and the intracellular calcium levels in the platelets. Methods: Heart rate and blood pressure were estimated using electrophysiology equipment. Results: While thrombin was unable to significantly affect the heart rate and blood pressure, the inhibitor dabigatran was able to reduce the heart rate appreciably but its effects on the blood pressure were minimal. The thrombin induced increase in PLC enzyme activity, and intracellular calcium levels were attenuated by dabigatran in the platelets. The posterior pituitary hormone, vasopressin, and the adrenergic agonist noradrenaline were used to stimulate the PLC and calcium levels in platelets. Conclusion: The thrombin inhibitor, dabigatran reduces vascular oxidative stress and inflammation, improves endothelial function, and decreases atherosclerosis in rodents.