title: Angiotensin II type AT(2) receptor mRNA expression and renal vasodilatation are increased in renal failure.
abstract: Kidney failure is associated with changes in renal vascular responses to angiotensin (Ang) II. We characterized expression of Ang II receptors and the renal vasoconstrictor and vasodilator responses to Ang II in kidneys from sham-operated and kidney failure rats. In the isolated perfused kidney of sham-operated rats, Ang II (1, 2, 4, and 8 ng) increased perfusion pressure by 27+/-6, 41+/-10, 54+/-11, and 74+/-12 mm Hg, respectively. These responses were amplified by 62+/-10% (P<0.05) in kidney failure rats. Losartan (1 micromol/L), an angiotensin type 1 (AT(1)) receptor blocker, abolished renal vasoconstriction induced by Ang II, unmasking a renal vasodilatation that was greater in kidney failure rats. CGP-42112 (1 micromol/L) or PD 123,319 (1 micromol/L), angiotensin type 2 (AT(2)) receptor ligands, blunted Ang II-induced renal vasodilatation. In the renal tissue of kidney failure rats, there was a marked increase in expression of AT(1) and AT(2) mRNA receptor. Ang II-induced vasodilatation was blunted by eicosatetraynoic acid (1 micromol/L), the all-purpose inhibitor of arachidonic acid metabolism; clotrimazole (1 micromol/L), an inhibitor of epoxygenase-dependent arachidonic acid metabolism; or Nomega-nitro-L-arginine methyl ester (L-NAME; 1 micromol/L), an inhibitor of NO synthesis. On stimulation with Ang II, 20-HETE was the predominant product released into the renal effluent of sham-operated rats, whereas epoxy-eicosatrienoic acids were the predominant products released into the effluent of kidney failure rats. These data suggest that during development of kidney failure, there is induction of the AT(2) receptors, which may account for increased Ang II-dependent vasodilatation through the predominant release of epoxyeicosatrienoic acids.
authors.affiliation: Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN, México.
authors.forename: R
authors.initials: R
authors.lastname: Bautista
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
authors.forename: J
authors.initials: J
authors.lastname: Hernández
authors.forename: A
authors.initials: A
authors.lastname: Oyekan
authors.forename: B
authors.initials: B
authors.lastname: Escalante
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D003022:Clotrimazole / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015117:5,8,11,14-Eicosatetraynoic Acid; C060894:CGP 42112A; C073402:PD 123319; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003577:Cytochrome P-450 Enzyme System; D003022:Clotrimazole; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin