The effects of centrally administered uridine and uridine nuclotides on cardiovascular parameters

Uridine is an endogenous nucleoside which exists freely in the circulation or within the structure of nucleotides. In this study, we aimed to investigate the effects of intracerebroventricularly (i.c.v.) administered uridine and its nucleotides on cardiovascular parameters and possible mechanisms of action. In the study, 4-6 months old male Sprague Dawley rats (n=120) were used. To analyze cardiovascular effects uridine, UMP, UDP and UTP were applied in three different doses as 0.1, 0.5 and 1 micromol (μmol). Blood pressure and heart rate values were recorded for 60 minutes. To investigate mechanism of action, P2Y receptor antagonists (MRS2578, PPTN hydrochloride and ARC-118925xx) were injected i.c.v. 15 minutes before the injection of the most effective dose of uridine nucleotides and blood pressure and heart rate were recorded. In addition, blood was collected via the catheter at 0, 5, 10, 30 and 60 minutes for catecholamines, oxytocin and vasopressin analyses. No significant effect of uridine and UMP on blood pressure and heart rate was found. While UDP and UTP did not change heart rate in dose-response groups, they increased blood pressure significantly in a dose-dependent manner. Pretreatment with P2Y receptor antagonists reversed the blood pressure increase achieved at the most effective dose (1 μmol). Serum vasopressin and oxytocin levels increased significantly at the most effective dose of UDP and UTP, while catecholamine levels did not change. The results of our study show for the first time in the literature that centrally administered UDP and UTP significantly increase blood pressure in rats and that these increases are associated with P2Y receptor activation. The effects observed are likely to be associated with increases in vasopressin and oxytocin levels. Our findings suggest that pyrimidinergic receptor activation may be an important mechanism in central regulation of blood pressure. Key words: Uridine, uridine nucleotides, blood pressure, heart rate, P2Y receptors