title: Contribution of bradykinin B2 receptors to the inhibition by valsartan of systemic and renal effects of exogenous angiotensin II in salt-repleted humans.
abstract: To investigate whether bradykinin (BK) participates in the inhibition of renal effects of exogenous angiotensin II (AngII) by AngII type 1 receptor (AT1R) blockade, eight salt-repleted volunteers underwent four p-aminohippurate- and inulin-based renal studies of AngII infusion at increasing rates of 0.625, 1.25, and 2.5 ng.kg.min(-1) for 30 min. Studies 1 and 2 were preceded by 3 days of placebo, whereas studies 3 and 4 used 240 to 320 mg.day(-1) valsartan. Bradykinin B2-type receptor (BKB2R) antagonist icatibant (50 mug.kg(-1)) was coinfused in studies 2 and 4. Mean blood pressure (MBP), glomerular filtration rate (GFR), renal blood flow (RBF), and renal sodium excretion (UNaV) were measured. In study 1, MBP rose by 12.8%, UNaV decreased by 68%, and GFR and RBF also fell (p < 0.001 for all). In study 2, GFR and RBF fell as in study 1, but the rise in MBP and the fall in UNaV were accentuated [+20.0%, analysis of variance (ANOVA), p < 0.02 versus study 1 and -80.0%, p < 0.05, respectively]. In study 3, AngII had no effects, and in study 4, renal hemodynamics remained unaffected, but MBP still rose and UNaV fell (ANOVA, p < 0.02 and 0.005 versus study 3, respectively). Icatibant accentuated AngII-induced changes in MBP and UNaV. Previous AT1R blockade prevented any systemic and renal effects of AngII, but significant changes in MBP and UNaV still followed AngII plus icatibant even after AT1R blockade. BK, through BKB2Rs, participates in the inhibitory action of AT1R blockers toward actions of exogenous AngII on MBP and UNaV in healthy humans.
authors.affiliation: Department of Clinical Sciences, University of Parma Medical School, Parma, Italy.
authors.forename: Almerina
authors.initials: A
authors.lastname: Biggi
authors.forename: Luisa
authors.initials: L
authors.lastname: Musiari
authors.forename: Matteo
authors.initials: M
authors.lastname: Iori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Iaco
authors.forename: Giulia
authors.initials: G
authors.lastname: Magnani
authors.forename: Irene
authors.initials: I
authors.lastname: Pelloni
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Pelà
authors.forename: Almerico
authors.initials: A
authors.lastname: Novarini
authors.forename: Aderville
authors.initials: A
authors.lastname: Cabassi
authors.forename: Alberto
authors.initials: A
authors.lastname: Montanari
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007444:Inulin; D007668:Kidney / Q000187:drug effects*; D008297:Male; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D010130:p-Aminohippuric Acid
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D065094:Bradykinin B2 Receptor Antagonists; D007202:Indicators and Reagents; D043782:Receptor, Bradykinin B2; D013777:Tetrazoles; D000804:Angiotensin II; C065679:icatibant; D000068756:Valsartan; D007444:Inulin; D012964:Sodium; D014633:Valine; D001920:Bradykinin; D010130:p-Aminohippuric Acid