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- Title
Uridine adenosine tetraphosphate affects contractility of mouse aorta and decreases blood pressure in conscious rats and mice.
- Authors
Hansen, P. B.; Hristovska, A.; Wolff, H.; Vanhoutte, P.; Jensen, B. L.; Bie, P.
- Abstract
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.
- Subjects
URIDINE; ADENOSINES; PHOSPHATES; CONTRACTILITY (Biology); REGULATION of blood pressure
- Publication
Acta Physiologica, 2010, Vol 200, Issue 2, p171
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/j.1748-1716.2010.02135.x