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 approximately 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) molL(-1) (18 ± 2% and 76 (+/-) 16% respectively); unexpectedly, 10(-5) molL(-1) caused a biphasic response with a contraction (19 6(+/-)2%) followed by a relaxation (-46 (+/-) 6%). No relaxation was observed when the concentration was increased further. Bolus exposure to 10(-5) molL(-1) of Up(4) A caused contraction (+80 (+/-) 2%). Added successively to untreated vessels, increasing concentrations of Up(4) A (10(-7) -10(-5) molL(-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.