Uridine adenosine tetraphosphate affects contractility of mouse aorta and decreases blood pressure in conscious rats and mice

Aim: In the anaesthetized rat, uridine adenosine tetraphosphate (Up(4)A) is a circulating, endothelium-derived vasoconstrictor presumably operating as such in un-anaesthetized animals. The present study investigated the in vivo effects of Up(4)A in conscious mice and rats, and its direct vascular effects in the mouse aorta in vitro. Methods: In vivo, Up(4)A was given as step-up infusion at rates of 8-512 nmol min-1 kg-1 for 30 min periods in chronically catheterized rodents. In vitro, the effect of Up(4)A on rings of mouse aortae mounted in a myograph was tested. Results: High doses of Up(4)A (mice: 512 nmol min-1 kg-1; rats: 128 nmol min-1 kg-1) caused hypotension (99 +/- 4 to 64 +/- 7 mmHg and 114 +/- 3 to 108 +/- 3 mmHg, respectively, both P < 0.01). In rats, Up(4)A significantly decreased sodium excretion by > 75% and potassium excretion by similar to 60% without significant changes in urine flow. Exposure of phenylephrine-contracted rings to increasing concentrations of Up(4)A elicited contraction at 10-7 and 10-6 mol L-1 (18 +/- 2% and 76 +/- 16% respectively); unexpectedly, 10-5 mol L-1 caused a biphasic response with a contraction (19 +/- 6%) followed by a relaxation (-46 +/- 6%). No relaxation was observed when the concentration was increased further. Bolus exposure to 10-5 mol L-1 of Up(4)A caused contraction (+80 +/- 2%). Added successively to untreated vessels, increasing concentrations of Up(4)A (10-7-10-5 mol L-1) induced a biphasic response of contraction followed by relaxation. Conclusion: Up(4)A has direct biphasic effects on vascular smooth muscle of the mouse aorta but vasoconstriction dominates at low concentrations. In conscious rodents, step-up infusions of Up(4)A elicit hypotension and electrolyte retention.