Evidence of α1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease

M. P. Cruz-Domínguez, R. Villalobos-Molina, A. Miliar-García, D. H. Montes-Cortés, A. C. Reséndiz-Ramírez, J. Asbun-Bojalil, J. Cervantes-Cruz, M. C. Castillo-Hernández, C. Castillo-Henkel

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

2 Citas (Scopus)

Resumen

1. α1-Adrenoceptor (α1-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 α1-AR competitive antagonists: 5-methylurapidil (α1A-), AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol; α1B- ) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4.5] decane-7,9-dione; α1D-). The relative abundance of mRNA for all three α1-ARs was determined. 4. The maximal contractile responses to phenylephrine were: Emax 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 α1A-AR antagonist (pA2: control 7.45, ESRD 8.36, ESRD-DM 8.0; P < 0.01), and a reduction in the α1B-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 α 1D-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 α1B-ARs and reduced both α1A- and α1D-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 α1-AR changes.

Idioma originalInglés
Páginas (desde-hasta)19-27
Número de páginas9
PublicaciónAutonomic and Autacoid Pharmacology
Volumen28
N.º1
DOI
EstadoPublicada - ene. 2008

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