title: Contribution of adenosine receptors in the control of arteriolar tone and adenosine-angiotensin II interaction.
abstract: Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II), which is important for renal hemodynamics and tubuloglomerular feedback (TGF). The aim was to investigate the function of Ado receptors in the Ado-Ang II interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4) mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado 10(-11)-10(-9) mol/l and returned to control values at higher concentrations. Treatment with Ang II (10(-10) mol/l) transformed the response into a concentration-dependent constriction. N(6)-cyclopentyladenosine (A(1)-Ado receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by 13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response. Afferent arterioles of mice lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado (10(-5) mol/l) did not influence the Ang II response, but an additional blockade of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II. Both directions of Ado-Ang II interaction, which predominantly leads to an amplification of the contractile response, are important for the operation of the TGF.
authors.affiliation: Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden.
authors.forename: E Y
authors.initials: EY
authors.lastname: Lai
authors.forename: A
authors.initials: A
authors.lastname: Patzak
authors.forename: A
authors.initials: A
authors.lastname: Steege
authors.forename: R
authors.initials: R
authors.lastname: Mrowka
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Spielmann
authors.forename: P B
authors.initials: PB
authors.lastname: Persson
authors.forename: B B
authors.initials: BB
authors.lastname: Fredholm
authors.forename: A E G
authors.initials: AE
authors.lastname: Persson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D005260:Female; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology*; D007684:Kidney Tubules / Q000098:blood supply / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010627:Phenethylamines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000502:physiology*; D043683:Receptors, Adenosine A2 / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; C496145:N-(4-acetylphenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy)acetamide; D010627:Phenethylamines; D011687:Purines; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D000804:Angiotensin II; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C053907:8-cyclopentyl-1,3-dimethylxanthine; C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; D000241:Adenosine