Disease relevance of BQ 123

• In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar [1].
• The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension [2].
• The inhibition of insulin-stimulated PI 3-kinase activity by ET-1 was prevented by BQ-123, a selective ET(A) receptor antagonist, but was not affected by pertussis toxin [3].
• Before applying the "NO clamp", BQ-123 caused an increase in FBF in both groups (p<0.001) that was greater in patients with cirrhosis (p<0.01) [4].
• Effect of BQ-123 and tissue plasminogen activator on vasospasm after subarachnoid hemorrhage in monkeys [5].

High impact information on BQ 123

• Chronic BQ 123 treatment attenuated the rise in mean pulmonary artery pressure (PAP) 8 d after ductus arteriosus ligation (78+/-2, HTN vs. 70+/-4 mmHg, BQ 123, P < 0.05) [6].
• Chronic BQ 123 treatment prevented the development of RVH as determined by the ratio of the right ventricle/left ventricle + septum (0.79+/-0.03, HTN vs. 0.57+/-0.06, BQ 123, P < 0.05) and attenuated the increase in wall thickness of small pulmonary arteries (61+/-2, HTN vs. 50+/-2%, BQ 123, P < 0.05) [6].
• To test this hypothesis, we studied the effects of BQ 123, a selective ET(A) receptor antagonist, after ligation of the ductus arteriosus in utero [6].
• SRTX-C was as potent as ET-1, while BQ 123 did not affect ET-1-induced growth inhibition [7].
• BQ-123 had no effect on the response to ET-3 (10(-8) M) [8].

Chemical compound and disease context of BQ 123

• In endothelium-intact aortic rings from rats exposed to 16-h hypoxia incubated with endothelin A receptor-specific antagonist BQ-123 (10(-7) M), SnPP IX did not alter phenylephrine-induced contraction [9].
• This effect is inhibited by BQ-123 (10 nmol) but not by BQ-788 (10 nmol).Thus, local ET-1 induces nocifensive behavior and thermal hyperalgesia acting through ET(A) receptors [10].
• Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys [11].
• RESULTS: Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to hyperglycemia and simulated ischemia-reperfusion injury (P =.01); this effect was prevented with both BQ-123 and bosentan (P =.01) [12].
• METHODS: The selective ET-A receptor blocker BQ-123 (10 and 50 nmol/min) was infused into the brachial artery, alone or in combination with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) (2 and 4 micromol/min) in 10 lung transplant recipients without pharmacologically treated hypertension and 8 healthy controls [13].

Biological context of BQ 123

• To determine whether big-endothelin-1 (big-ET-1)-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123 [14].
• Nitro-L-arginine (L-NA), a selective endothelium-derived nitric oxide (EDNO) antagonist, blocked vasodilation caused by BQ 123 and SFX [14].
• In contrast, BQ 123 did not change vascular resistance in a regional systemic circulation (the fetal hindlimb) [14].
• To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs [14].
• BQ-788, but not BQ-123, facilitated peristalsis on its own [15].

Anatomical context of BQ 123

• Brief intrapulmonary infusions of BQ 123 (0.1-1.0 mcg/min for 10 min) caused sustained increases in left pulmonary artery flow (Qp) without changing main pulmonary artery (MPA) and aortic (Ao) pressures [14].
• Addition of superoxide dismutase plus catalase or an antagonist of endothelin-A receptors (BQ-123) reduced contractions in rings with endothelium but not in those without endothelium to suspensions of mononuclear cells from rejecting allotransplanted dogs [16].
• Brachial artery infusion of BQ-123 caused significant forearm vasodilatation in both studies [17].
• The present study, in human forearm resistance vessels in vivo, was designed to further investigate the physiological function of ET(A) and ET(B) receptor subtypes in human blood vessels and determine the mechanism underlying the vasodilatation to the ET(A)-selective receptor antagonist BQ-123 [17].
• To characterize the ET receptors present in dog coronary arteries, competition binding assays with radiolabeled ET-1 using ET-1, ET-3, ETA receptor antagonist BQ-123, and sarafotoxin S6c were performed [18].

Associations of BQ 123 with other chemical compounds

• We examined the contribution of endogenously generated endothelin-1 to maintenance of peripheral vascular tone in healthy subjects by local intraarterial administration of an inhibitor of endothelin converting enzyme, phosphoramidon, and of a selective endothelin receptor A antagonist, BQ-123 [19].
• METHODS AND RESULTS: In endothelium-denuded IMA and PCA and less so in IMV, FR139317 and BQ-123 (in PCA only) shifted the concentration-contraction curves to ET-1 parallel to the right [20].
• Interestingly, the positive inotropic effect was completely blocked by selectively damaging endocardial endothelium (Triton X-100, 0.5%, 1-s immersion, n = 7) before ROS generation and by preincubating the muscles with the endothelin-A receptor antagonist BQ 123 (n = 11) [21].
• CsA elevated blood pressure 17 to 20% in all three groups; renal resistance maximally increased 23, 20, and 23% in vehicle, BQ-123, and BQ-123 and PD 142893 pretreated groups, respectively [22].
• In one study, six subjects received placebo, the ETA receptor antagonist BQ-123 alone, and BQ-123 in combination with the ETB receptor antagonist BQ-788 after pretreatment with the ACE inhibitor enalapril (E) or placebo [23].

Gene context of BQ 123

• The specificity of the cardiovascular response to endothelin was demonstrated by the inhibitory effects of the receptor antagonist BQ-123 [24].
• BQ 123, a selective ETAR antagonist, blocked the ET-1-induced Cx43 phosphorylation and cellular uncoupling [25].
• METHODS: Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intra-arterial infusion of a selective blocker of ETA receptors (BQ-123) and, on a separate occasion, to ET-1 were measured in 12 hypercholesterolemic patients and 12 normal control subjects [26].
• BQ-123, an ETA blocker, completely blocked the responsiveness of the MAP kinase to either ET-1 or ET-3 [27].
• In addition, on a different day, six hypercholesterolemic patients received co-infusion of BQ- 123 and BQ-788 (a selective blocker of ETB receptors) [26].

Analytical, diagnostic and therapeutic context of BQ 123

• BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period [28].
• ET-1 increased the perfusion pressure of collaterals and its effect was significantly suppressed by BQ-123 alone and BQ-123 plus BQ-788, but not BQ-788 alone (P <.05) [29].
• Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET(B) receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography [30].
• RESULTS: Intra-arterial infusion of ET-1 significantly increased iliac PWV by 12 +/- 5% (mean +/- STD; p < 0.001), whereas infusion of the endothelin-A (ET(A)) receptor antagonist BQ-123 significantly reduced PWV by 12 +/- 4% (p < 0.001) [31].
• After 6 weeks of untreated diabetes, rats were implanted with osmotic minipumps which continuously delivered the endothelin-1 antagonist, BQ-123, to the circulation via a jugular vein cannula [32].

References