Disease relevance of BQ-610

• ET-induced myocardial ischemia was abolished by molsidomine and BQ 610 [1].
• Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension [2].
• The stimulatory effect of 20 nM ET-1 on these channels was markedly attenuated in the presence of the selective ET(A) receptor antagonist BQ-610 (200 nM), or after pertussis toxin (200 ng/ml, 16 h) pretreatment [3].
• In protocol 3, CR progressively increased with hypotension in the absence but not presence of l-NAME or BQ-610 [4].
• Our studies showed that insulin infusion caused sustained hyperinsulinemia in both saline- and BQ-610-injected rats over the infusion period [5].

High impact information on BQ-610

• Cotreatment with the ETA receptor antagonist BQ 610 prevented these effects, whereas inhibitors of G alpha i or G beta gamma were without effect [6].
• Indeed, blockade of ETA endothelin receptors with BQ-610 (1 microM), similar to removal of the endothelium and alpha5 integrin blockade, inhibited the vasoconstriction [7].
• The ETA receptor-selective antagonist BQ 610, the novel ETA-receptor antagonist ETR-PI/fl peptide, and the ETB-receptor antagonist IRL 1038 were used to investigate the roles of receptor subtypes [8].
• ETR-PI/fl peptide inhibited leukocyte rolling by 88%, BQ 610 by 73%, and IRL 1038 by 30% [8].
• Inotropic effects of endothelin-1: interaction with molsidomine and with BQ 610 [1].

Chemical compound and disease context of BQ-610

• Forty-five isolated rat hearts were perfused with Krebs-Henseleit buffer (KHB) for 15 min and then subjected to 0, 15, or 60 min of ischemia followed by 5 min of reperfusion with KHB, KHB + BQ-610, or KHB + BQ-123 [9].

Biological context of BQ-610

• Pretreatment with molsidomine and BQ 610 attenuated the ET-induced reduction of cardiac output (ET-1: -62%; molsidomine+ET-1: -47%; BQ 610+ET-1: -27% different from controls) [1].
• Neither antagonist significantly modified the ET-1-induced changes in tumour blood flow or vascular resistance, whereas in the majority of normal tissues BQ-610 attenuated and BQ-788 potentiated the vascular resonse to ET-1 [10].
• No significant changes were found in insulin sensitivity and blood pressure in saline-infused rats treated with BQ-610 [5].
• This response was blunted by reactive oxygen species (ROS) scavengers (mannitol and superoxide dismutase plus catalase) and was converted into vasodilation by l-NAME, BQ-610, or BQ-788 [4].
• BQ-610 in 6 animals renal blood flow increased (2.3 +/- 0.7 ml. per minute per kg., p < 0.05) and mean arterial blood pressure decreased (-2.7 +/- 0.3 mm. Hg, p < 0.05 versus vehicle) [11].

Anatomical context of BQ-610

• Study of microcirculation by coloured microspheres and NMR-microscopy in isolated rat heart: effect of ischaemia, endothelin-1 and endothelin-1 antagonist BQ 610 [12].
• 4. Pre-incubation of the trachea with BQ-610 (1 microM) or indomethacin (1 microM) prevented cyclicAMP formation by either ET-1 or ET-3 [13].
• By comparison, the ET(A) receptor antagonist BQ-610 at 1 micromol/l produced a much more potent inhibitory effect (three-order shifting) on endothelin-1-induced contraction in internal mammary arteries, and also potently inhibited the contraction in radial arteries [14].
• ET-1, ET-3, IRL 1620, and BQ 610 inhibited [125I]ET-binding to the rat ureter consistent with the predominance of ETA receptors in these tissues [15].
• Treatment of corresponding groups with BQ-610 increased the proportion of competent capillaries but these differences were not statistically significant [9].

Associations of BQ-610 with other chemical compounds

• Endothelin receptor subtypes were characterized in isolated perfused rat lungs using the peptide ETA-receptor antagonists BQ 610 and BQ 123, the nonpeptide mixed ETA-/ETB-receptor antagonist bosentan, and the ETB-receptor agonist IRL 1620 [16].
• The ET-1-induced release of 6-keto-PGF1 alpha was blocked by bosentan, but not by BQ 610 [16].
• Oral glucose tolerance tests showed that BQ-610 treatment did not prevent the insulin resistance caused by chronic insulin infusion [5].
• The inhibitory effects of ET-1 on secretin-induced cAMP synthesis and luminal duct expansion were blocked by specific inhibitors of the ETA (BQ-610) receptor [17].

Gene context of BQ-610

• In addition, BQ 610, an ETA receptor subtype antagonist, inhibited ET-1-induced cAMP accumulation in a dose-dependent manner (IC50s for bovine and cat were 11 and 19.5 nM, respectively) [18].
• Results showed that ETs-stimulated NOS activity was inhibited by a selective ETB antagonist (BQ-788), but not by a selective ETA antagonist (BQ-610) [19].
• The specific ET(A) receptor antagonist, BQ-610 (1 microM), significantly inhibited ET-1-stimulated adiponectin secretion [20].
• Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective [21].
• We hypothesized that ET(A) blockers (EMD 122946 and BQ 610) would reduce hypoxia-induced (HYP) but not group B streptococcal infusion (GBS)-induced pulmonary hypertension in a juvenile whole animal model [22].

Analytical, diagnostic and therapeutic context of BQ-610

• In group 4, BQ 610 had no effect on perfusion nor on vessel size and antagonized the effect of endothelin-1 on perfusion and vessel size in group 5 [12].
• Intravascular infusion of Fg induced significant constriction of 3As and 2As (by 33.4 +/- 3.4 and 23.7 +/- 4.3%, respectively) in vivo and was abolished in the presence of the specific endothelin type A receptor blocker BQ-610 [23].
• The local microvascular perfusion, measured by the arterio-venous transit time, was improved during reperfusion by BQ 610 (1.3+/-0.5 s in the control vs. 0.7+/-0.2 s in the experimental group, P<0.05) [24].
• To study the role of ET(A) receptors under these pathophysiological conditions, one group was treated with the ET(A) antagonist BQ 610 (0.8 micromol/l) during hypoperfusion, and compared with a control group which received a saline infusion during hypoperfusion [25].
• Moreover, BQ-123 and BQ-610, when administered alone, evoked a significant decrease in the mitotic index [26].

References