Stimulation of the A₁ adenosine receptor and angiotensin II receptor type‐1 (AT₁ receptor) causes vasoconstriction through activation of cytochrome P450 4A (CYP4A) and ERK1/2. Thus, we hypothesized that acute angiotensin II activation alters the vasomotor response induced by the non‐selective adenosine receptor agonist, NECA, in mouse mesenteric arteries (MAs).

We used a Danish Myo Technology wire myograph to measure muscle tension in isolated MAs from wild type (WT), A₁ receptor and A_2B receptor knockout (KO) mice. Western blots were performed to determine the expression of AT₁ receptors and CYP4A.

Acute exposure (15 min) to angiotensin II attenuated the NECA‐dependent vasodilatation and enhanced vasoconstriction. This vasoconstrictor effect of angiotensin II in NECA‐treated MAs was abolished in A₁ receptor KO mice and in WT mice treated with the A₁ receptor antagonist DPCPX, CYP4A inhibitor HET0016 and ERK1/2 inhibitor PD98059. In MAs from A_2B receptor KO mice, the vasoconstrictor effect of angiotensin II on the NECA‐induced response was shown to be dependent on A₁ receptors. Furthermore, in A_2B receptor KO mice, the expression of AT₁ receptors and CYP4A was increased and the angiotensin II‐induced vasoconstriction enhanced. In addition, inhibition of K_ATP channels with glibenclamide significantly reduced NECA‐induced vasodilatation in WT mice.

Acute angiotensin II stimulation enhanced A₁ receptor‐dependent vasoconstriction and inhibited A_2B receptor‐dependent vasodilatation, leading to a net vasoconstriction and altered vasomotor response to NECA in MAs. This interaction may be important in the regulation of BP.