TY - JOUR
T1 - Evidence of α1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease
AU - Cruz-Domínguez, M. P.
AU - Villalobos-Molina, R.
AU - Miliar-García, A.
AU - Montes-Cortés, D. H.
AU - Reséndiz-Ramírez, A. C.
AU - Asbun-Bojalil, J.
AU - Cervantes-Cruz, J.
AU - Castillo-Hernández, M. C.
AU - Castillo-Henkel, C.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Human omental arteries
KW - Renal disease
KW - Vascular reactivity
KW - α-adrenoceptors
UR - http://www.scopus.com/inward/record.url?scp=38949088978&partnerID=8YFLogxK
U2 - 10.1111/j.1474-8673.2007.00413.x
DO - 10.1111/j.1474-8673.2007.00413.x
M3 - Artículo
SN - 1474-8665
VL - 28
SP - 19
EP - 27
JO - Autonomic and Autacoid Pharmacology
JF - Autonomic and Autacoid Pharmacology
IS - 1
ER -