Adenosine A(1) receptors and vascular reactivity.
OBJECTIVE
Blood pressure is higher in A(1) receptor knock-out (A(1)R-/-) mice than in wild type litter mates (A(1)R+/+) and we have examined if this could be related to altered vascular functions.


METHODS
Contraction of aortic rings and mesenteric arteries were examined. To examine if the adenosine A(1) receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients.


RESULTS
Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N-ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A(1)R-/- mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A(2B) adenosine receptors, rather than A(2A) receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A(1)R-/- mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A(1)R-/- mice.


CONCLUSIONS
The role of adenosine A(1) receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A(1) knock-out mice. The A(1) receptor modulation of blood pressure is therefore mainly related to extravascular factors.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Y
Y
Wang
J N
JN
Yang
A
A
Arner
P J M
PJ
Boels
B B
BB
Fredholm
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D043682:Receptor, Adenosine A1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D000241:Adenosine; D000109:Acetylcholine