Evidence of α₁‐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.

Differential regulation of nitric oxide synthase function in aorta and tail artery from 5/6 nephrectomized rats

“…Furthermore, omental arteries from patients with kidney disease have an augmented vasoconstriction response to the α 1 ‐adrenoceptor agonist phenylephrine (PE) (Cruz‐Dominguez et al. ). These changes in vascular function have been attributed to several risk factors, not the least of which is hypertension (Guerin et al.…”

“…Notably endothelial dysfunction, which is classically detected as a blunted acetylcholine (ACh)-induced vasorelaxation response, is a consistent finding as demonstrated in omental arteries from patients with end-stage renal disease (Annuk et al 2001;Luksha et al 2012). Furthermore, omental arteries from patients with kidney disease have an augmented vasoconstriction response to the a 1 -adrenoceptor agonist phenylephrine (PE) (Cruz-Dominguez et al 2008). These changes in vascular function have been attributed to several risk factors, not the least of which is hypertension (Guerin et al 2008).…”

Cinética de la tensión aórtica torácica inducida con fenilefrina en rata macho durante crecimiento y desarrollo

“…Los animales, anestesiados, se desangraron 17 . El AoTx[EF] se colocó en solución de bicarbonato de Krebs-Ringer (RK) oxigenada fría para obtener anillos de 4 a 5 mm de longitud que fueron montados en baños de 10 ml para tejido en la solución RK mantenidos a 37 ºC, pH 7.4, y gaseado continuamente con 95% de O 2 y 5% de CO 2 15 para su bioensayo 14,18 . El valor de la transición de la tensión de la contracción isométrica hacia el estado asintótico (T[On]) se midió con un transductor de desplazamiento de fuerza modelo 1030 (UFI) y se registró en línea con el software AcqKnowledge (MP100WSW; Biopac Sistema, Inc., Santa Barbara, California, EE.UU.)…”

“…El valor de la transición de la tensión de la contracción isométrica hacia el estado asintótico (T[On]) se midió con un transductor de desplazamiento de fuerza modelo 1030 (UFI) y se registró en línea con el software AcqKnowledge (MP100WSW; Biopac Sistema, Inc., Santa Barbara, California, EE.UU.) 14,18 .…”

“…Previa línea de referencia de precontracción (LRPreC) AoTx se adicionó 1 μM de FE al baño del tejido para obtener la T[On] experimental a FE. La EF se verificó por la presencia de al menos un 80% de relajación en respuesta a 1 μM de Acth después de preconstreñir los tejidos con 1 μM de FE 18 .…”