title: Evidence of alpha1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease.
abstract: 1 Alpha1-Adrenoceptor (alpha1-AR) subtypes were characterized in isolated omental arteries obtained after abdominal surgery in patients with end-stage renal disease (ESRD) or with Diabetes Mellitus type 2 plus ESRD (ESRD-DM). 2 Omental arteries from patients with ESRD and ESRD-DM elicited a significant increase in sensitivity to phenylephrine with a pD(2) (-log EC50) of 6.7 and 6.6, respectively, vs. the control (5.8, P < 0.001). 3 Stimulation with phenylephrine was conducted in the presence or absence of selective alpha1-AR competitive antagonists: 5-methylurapidil (alpha1A-), AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol; alpha1B-) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4.5] decane-7,9-dione; alpha(1D)-). The relative abundance of mRNA for all three alpha(1)-ARs was determined. 4 The maximal contractile responses to phenylephrine were: E(max) 1.59 +/- 0.17, 1.48 +/- 0.08 and 1.55 +/- 0.14 g for the ESRD, ESRD-DM and control groups, respectively. 5 Functionally, there was an increment in the affinity for the alpha(1A)-AR antagonist (pA2: control 7.45, ESRD 8.36, ESRD-DM 8.0; P < 0.01), and a reduction in the alpha1B-AR antagonist affinity (8.3 for controls, 7.6 for ESRD and 7.3 for ESRD-DM; P < 0.01) associated with renal disease. The affinities for the alpha1D-AR antagonist were similar among the studied groups (8.5 for the controls, 8.7 for the ESRD and 8.1 for the ESRD-DM groups). 6 Renal disease increased mRNA expression of alpha(1B)-ARs and reduced both alpha1A- and alpha(1D)-ARs subtypes in ESRD and ESRD-DM patients. 7 The results suggest that human omental arteries exposed to chronic uraemia show vascular hypersensitivity to phenylephrine, because of functional alpha1-AR changes.
authors.affiliation: Hospital Centro Médico La Raza, Instituto Mexicano del Seguro Social, Seris y Zaachila s/n, México, D.F. 02990.
authors.forename: M P
authors.initials: MP
authors.lastname: Cruz-Domínguez
authors.forename: R
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: A
authors.initials: A
authors.lastname: Miliar-García
authors.forename: D H
authors.initials: DH
authors.lastname: Montes-Cortés
authors.forename: A C
authors.initials: AC
authors.lastname: Reséndiz-Ramírez
authors.forename: J
authors.initials: J
authors.lastname: Asbun-Bojalil
authors.forename: J
authors.initials: J
authors.lastname: Cervantes-Cruz
authors.forename: M C
authors.initials: MC
authors.lastname: Castillo-Hernández
authors.forename: C
authors.initials: C
authors.lastname: Castillo-Henkel
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007097:Imines / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009852:Omentum / Q000098:blood supply*; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; C434277:AH 11110A; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007097:Imines; D010879:Piperazines; D010880:Piperidines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C057446:5-methylurapidil; D010656:Phenylephrine; C053428:BMY 7378