Disease relevance of ETBR

• Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus [1].

High impact information on ETBR

• Plasma endothelin-1 and cGMP levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin-converting enzyme-1, endothelin A, and endothelin B receptor protein levels were similar in both groups [2].
• Ligation of the ductus arteriosus was also associated with increased expression of preproendothelin-1 mRNA and with decreased expression of endothelin B receptor (ET(B)) mRNA [3].
• 3. As expected, sheep isolated tracheal smooth muscle preparations did not contract in response to the ETB receptor-selective agonist, sarafotoxin S6c (0.1-100 nM) [4].
• The inhibitory effect induced by a maximally effective concentration of sarafotoxin S6c (10 nM; 72.1 +/- 5.7%, n = 6) was abolished in the presence of the ETB receptor-selective antagonist BQ-788 (1 microM) [4].
• 1. The relative roles of ETA and ETB receptor activation on cholinergic nerve-mediated contraction and acetylcholine (ACh) release were examined in sheep isolated tracheal smooth muscle [4].

Chemical compound and disease context of ETBR

• These findings suggest that increased ET-1 production and decreased ETB-receptor expression may contribute to increased vasoconstrictor tone in this experimental model of neonatal pulmonary hypertension [5].

Biological context of ETBR

• This study demonstrates that ETa receptor activation has a small role in maintaining basal fetal pulmonary vascular tone, and that specific ETb receptor activation produces marked pulmonary vasodilation [6].
• The infusion of Ro 47-0203 blocked the decrease in pulmonary vascular resistance induced by injections of either ET-1 (-0.985 versus +0.012 mm Hg/mL/min/100 g of lung, p < 0.05) or 4-Ala-ET-1 (an ETb receptor agonist) (-0.717 versus -0.052 mm Hg/mL/min/100 g of lung, p < 0.05) [7].
• This altered response to ET-1 is associated with decreased ETb receptor-mediated vasodilation and increased ETa receptor-mediated vasoconstriction [8].
• Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension [5].
• The possibility that significant changes in endothelin (ET)A- and ETB-receptor density and function occur in airway smooth muscle cells (ASMCs) during cell growth and extended cell culture was investigated in sheep tracheal ASMCs [9].

Anatomical context of ETBR

• Endothelin-1, via activation of an ETB receptor, inhibits cholinergic nerve-mediated contractions in sheep trachea [10].
• Chemical crosslinking of [125I]ET-1 with bis(sulfosuccinimidyl)-suberate (BS3) to choroid plexus membranes revealed the presence of two bands, with apparent molecular masses of 89 and 45 kDa, corresponding to the ETA receptor, and three bands, with apparent molecular masses of 75, 58, and 33 kDa, corresponding to the ETB receptor [11].
• In contrast, protein expression levels of ETA and ETB receptor were significantly lower in the vascular smooth muscle cells among other tissue subcompartments of the right lung of treated CDH newborn lambs vs CDH lambs (P < .02 and P = .005, respectively) [12].

Associations of ETBR with chemical compounds

• BQ 123 (1 microM) also abolished specific binding to structures associated with submucosal glands, whereas the ETB receptor selective agonist, sarafotoxin S6c (100 nM) had little effect on this binding, indicating the predominance of ETA receptors at these sites [13].
• Twelve sheep received S+B injury using the following protocol: six sheep were treated with tezosentan, an ETA and ETB receptor antagonist, and six sheep received an equivalent volume of vehicle [14].
• The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared [8].
• METHODS: The effect of atrasentan on protein expression levels of ETs and ET receptors (ETA and ETB receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8) [12].

Analytical, diagnostic and therapeutic context of ETBR

• OBJECTIVE AND METHODS: To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep [15].

References