Evidence of alpha1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease

• Published in: Autonomic & autacoid pharmacology Vol. 28; no. 1; pp. 19 - 27
• Main Authors: Cruz-Domínguez, M P, Villalobos-Molina, R, Miliar-García, A, Montes-Cortés, D H, Reséndiz-Ramírez, A C, Asbun-Bojalil, J, Cervantes-Cruz, J, Castillo-Hernández, M C, Castillo-Henkel, C
• Format: Journal Article
• Language: English
• Published: England 01.01.2008
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Adult; Arteries - metabolism; Arteries - physiopathology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Dose-Response Relationship, Drug; Female; Humans; Imines - pharmacology; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - physiopathology; Male; Middle Aged; Omentum - blood supply; Phenylephrine - pharmacology; Piperazines - pharmacology; Piperidines - pharmacology; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - genetics; Receptors, Adrenergic, alpha-1 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology
• ISSN: 1474-8673
• DOI: 10.1111/j.1474-8673.2007.00413.x

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.