title: Angiotensin II enhances the afferent arteriolar response to adenosine through increases in cytosolic calcium.
abstract: OBJECTIVE
  Angiotensin II (Ang II) is a strong renal vasoconstrictor and modulates the tubuloglomerular feedback (TGF). We hypothesized that Ang II at low concentrations enhances the vasoconstrictor effect of adenosine (Ado), the mediator of TGF.
  
  
  METHODS
  Afferent arterioles of mice were isolated and perfused, and both isotonic contractions and cytosolic calcium transients were measured.
  
  
  RESULTS
  Bolus application of Ang II (10(-12) and 10(-10) M) induced negligible vasoconstrictions, while Ang II at 10(-8) m reduced diameters by 35%. Ang II at 10(-12), 10(-10) and 10(-8) m clearly enhanced the arteriolar response to cumulative applications of Ado (10(-11) to 10(-4) M). Ado application increased the cytosolic calcium concentrations in the vascular smooth muscle, which were higher at 10(-5) M than at 10(-8) M. Ang II (10(-11) to 10(-6) M) also induced concentration-dependent calcium transients, which were attenuated by AT(1) receptor inhibition. Simultaneously applied Ang II (10(-10) M) additively enhanced the calcium transients induced by 10(-8) and 10(-5) M Ado. The transients were partly inhibited by AT(1) or A(1) receptor antagonists, but not significantly by A(2) receptor antagonists.
  
  
  CONCLUSIONS
  A low dose of Ang II enhances Ado-induced constrictions, partly via AT(1) receptor-mediated calcium increase. Ado increases intracellular calcium by acting on A(1) but not A(2) receptors. The potentiating effect of Ang II on Ado-induced arteriolar vasoconstrictions may involve calcium sensitization of the contractile machinery, as Ang II only additively increased cytosolic calcium concentrations, while its effect on the arteriolar constriction was more than additive. The potentiating effect of Ang II might contribute to the resetting of TGF.
authors.affiliation: Division of Physiology, Department of Medical Cell Biology, Uppsala University, S-75123 Uppsala, Sweden.
authors.forename: E Y
authors.initials: EY
authors.lastname: Lai
authors.forename: A
authors.initials: A
authors.lastname: Patzak
authors.forename: A E G
authors.initials: AE
authors.lastname: Persson
authors.forename: M
authors.initials: M
authors.lastname: Carlström
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000502:physiology*; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000804:Angiotensin II / Q000008:administration & dosage / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000737:chemistry / Q000187:drug effects; D002118:Calcium / Q000737:chemistry*; D003600:Cytosol / Q000737:chemistry*; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D009287:Naphthyridines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; C496145:N-(4-acetylphenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy)acetamide; D009287:Naphthyridines; D011687:Purines; D043682:Receptor, Adenosine A1; D044140:Receptor, Angiotensin, Type 1; D043683:Receptors, Adenosine A2; D014227:Triazines; D014230:Triazoles; C095905:ZD 7155; C097270:ZM 241385; D000804:Angiotensin II; D000241:Adenosine; D002118:Calcium