title: High-salt diet inhibits expression of angiotensin type 2 receptor in resistance arteries.
abstract: Recent studies suggested that type 2 angiotensin receptor (AT2R) could contribute to regulation of blood pressure and/or vascular remodeling. A key question relates to the effects of potential modulators of vascular AT2R expression. In the present work, we evaluated if high salt intake (70 mmol/L NaCl in drinking water) could modulate rat mesenteric artery AT2R function and expression. Angiotensin II dose-response curves were studied in rat perfused pressurized small-diameter arteries in the presence of losartan (AT1R antagonist). Arteries were precontracted with phenylephrine, yielding approximately 30% decrease in resting diameter. AT2R activation by angiotensin-induced dose-dependent relaxation of precontracted arteries (60.1+/-9.1% of phenylephrine-induced contraction, P<0.05). In contrast, AT2R-dependent relaxation was not observed in arteries obtained from rats on high-salt diet. Semi-quantitative reverse-transcription polymerase chain reaction experiments demonstrated reduced amount of AT2R mRNA in arteries of rats on high-salt diet (65.5+/-7.5% of control levels, P<0.05). Western blot studies demonstrated decreased AT2R in mesenteric artery protein fractions of high-salt diet rats (60.0+/-18.0 of control levels, P<0.05). In a second set of experiments, adrenalectomy (4 days) blunted AT2R-mediated vasorelaxation and decreased AT2R mRNA (72.0+/-11.0% of control levels, P<0.05). AT2R abundance in protein fractions of mesenteric arteries of ADX rats was also diminished (64.0+/-13% of control levels, P<0.05). Both, AT2R mRNA and protein downregulation were prevented by mineralocorticoid replacement therapy. Finally, physiological concentrations of aldosterone caused a dose-dependent increase in AT2R mRNA of small diameter mesenteric artery explants. The results are consistent with aldosterone-mediated upregulation AT2R.
authors.affiliation: Laboratory of Molecular and Integrative Physiology, Faculty of Medicine, University Los Andes, Chile.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Lorena
authors.initials: L
authors.lastname: Lobos
authors.forename: Felipe
authors.initials: F
authors.lastname: Castillo
authors.forename: Lorna
authors.initials: L
authors.lastname: Galleguillos
authors.forename: Nandy C
authors.initials: NC
authors.lastname: Lopez
authors.forename: Luis
authors.initials: L
authors.lastname: Michea
mesh_terms: D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D004573:Electrolytes; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D000450:Aldosterone