科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background and PurposeStimulation of the A(1) adenosine receptor and angiotensin II receptor type-1 (AT(1) 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). Experimental ApproachWe used a Danish Myo Technology wire myograph to measure muscle tension in isolated MAs from wild type (WT), A(1) receptor and A(2B) receptor knockout (KO) mice. Western blots were performed to determine the expression of AT(1) receptors and CYP4A. Key ResultsAcute exposure (15min) to angiotensin II attenuated the NECA-dependent vasodilatation and enhanced vasoconstriction. This vasoconstrictor effect of angiotensin II in NECA-treated MAs was abolished in A(1) receptor KO mice and in WT mice treated with the A(1) 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 A(1) receptors. Furthermore, in A(2B) receptor KO mice, the expression of AT(1) 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. Conclusions and ImplicationsAcute angiotensin II stimulation enhanced A(1) 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.
- 出版日期2015-10
