title: Angiotensin II stimulation alters vasomotor response to adenosine in mouse mesenteric artery: role for A1 and A2B adenosine receptors.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  We used a Danish Myo Technology wire myograph to measure muscle tension in isolated MAs from wild type (WT), A1 receptor and A2B receptor knockout (KO) mice. Western blots were performed to determine the expression of AT1 receptors and CYP4A.
  
  
  RESULTS
  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 A2B receptor KO mice, the vasoconstrictor effect of angiotensin II on the NECA-induced response was shown to be dependent on A1 receptors. Furthermore, in A2B receptor KO mice, the expression of AT1 receptors and CYP4A was increased and the angiotensin II-induced vasoconstriction enhanced. In addition, inhibition of KATP channels with glibenclamide significantly reduced NECA-induced vasodilatation in WT mice.
  
  
  CONCLUSIONS
  Acute angiotensin II stimulation enhanced A1 receptor-dependent vasoconstriction and inhibited A2B 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.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Morgantown, WV, USA.
authors.forename: Vishal R
authors.initials: VR
authors.lastname: Yadav
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV, USA.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Nayeem
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Morgantown, WV, USA.|West Virginia Center for Translational Science Institute, Morgantown, WV, USA.
authors.forename: S Jamal
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D042926:Cytochrome P-450 CYP4A / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D043704:Receptor, Adenosine A2B; D044140:Receptor, Angiotensin, Type 1; D014665:Vasodilator Agents; D000804:Angiotensin II; D019830:Adenosine-5'-(N-ethylcarboxamide); D042926:Cytochrome P-450 CYP4A; D000241:Adenosine