| Autor: |
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. |
| Předmět: |
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| Zdroj: |
Autonomic & Autacoid Pharmacology; Jan2008, Vol. 28 Issue 1, p19-27, 9p, 3 Charts, 5 Graphs |
| Abstrakt: |
1α1-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 pD2 (−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 α1D-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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