Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Aim: In the anaesthetized rat, uridine adenosine tetraphosphate (Up4A) is a circulating, endothelium‐derived vasoconstrictor presumably operating as such in un‐anaesthetized animals. The present study investigated the in vivo effects of Up4A in conscious mice and rats, and its direct vascular effects in the mouse aorta in vitro.
Methods: In vivo, Up4A 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 Up4A on rings of mouse aortae mounted in a myograph was tested.
Results: High doses of Up4A (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, Up4A significantly decreased sodium excretion by >75% and potassium excretion by ∼60% without significant changes in urine flow. Exposure of phenylephrine‐contracted rings to increasing concentrations of Up4A 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 Up4A caused contraction (+80 ± 2%). Added successively to untreated vessels, increasing concentrations of Up4A (10−7–10−5 mol L−1) induced a biphasic response of contraction followed by relaxation.
Conclusion: Up4A 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 Up4A elicit hypotension and electrolyte retention.