Disease relevance of FR139317

• METHODS: We administered either the ETA receptor antagonist FR139317 (FR [n = 8], 1 and 10 mg/kg body weight) or the ETB receptor antagonist RES-701-1 (RES [n = 8], 0.2 and 1.5 mg/kg) to dogs with CHF induced by rapid ventricular pacing [1].
• We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension [2].
• The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats [3].
• Administration of FR139317 to rats with experimental glomerulonephritis induced a significant reduction in mesangial cell proliferation [4].
• During hypoxaemia the rapid initial bradycardia, the increase in MABP and FVR and the decrease in FBF were similar with vehicle and FR139317 infusion [5].

High impact information on FR139317

• In the Ad.ET-1 group, intravenous infusion of the ET(A) receptor antagonist FR 139317 reduced the blood pressure to levels seen in the Ad.betaGal group, whereas the same antagonist did not significantly alter the blood pressure in the Ad.betaGal group [6].
• Acute endothelin A receptor blockade with FR-139317 resulted in significant decreases in mean arterial pressure and systemic vascular resistance in TIVCC [7].
• FR901533 and FR139317 decreased mean arterial pressure and pulmonary capillary wedge pressure associated with reduction in systemic and pulmonary vascular resistance [8].
• These drugs increased the urinary water and sodium excretion rate associated with increases in the glomerular filtration rate and renal plasma flow, and the incremental magnitude induced by FR139317 was larger than that by FR901533 (P<0.05) [8].
• Two incremental doses of a specific ECE inhibitor, FR901533, or a selective ETA receptor antagonist, FR139317 (1 and 3 mg/kg, n=8, respectively), were injected into dogs with CHF [8].

Chemical compound and disease context of FR139317

• Like BQ-123, FR 139317 (7.5, 75, and 750 pmol/paw) also inhibited OVA-induced edema in a graded fashion but was less potent [9].
• A marked decrease in vascular wall hypertrophy was observed in the FR139317-treated DOCA-salt rats [10].
• CONCLUSION: Selective ETA antagonist FR139317 improved the hemodynamics and reduced the plasma ET-1 level and the mortality of rats with congestive heart failure[11]

Biological context of FR139317

• This coronary vasoconstriction was substantially reversed by treatment either with antibody against TNF-alpha or with FR 139317 [12].
• An endothelin type A receptor antagonist, FR139317, negated the inhibitory effect of ET-1 on apoptosis, while the endothelin type B receptor antagonist BQ788 did not show such a negation [13].
• BQ123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) and FR139317 (cC6N-L-Leu-D-Trp-Me-D-2Pya-OH), two antagonists that are selective for the ETA receptor, inhibited 125I-ET-1 binding with IC50 values of 5 nM and 0.9 nM, respectively [14].
• The phosphatidylinositol hydrolysis response was also inhibited by BQ123 and FR139317 [14].
• In contrast, FR139317 showed low affinity for [125I]ET-1 specific binding sites in porcine kidney (IC50, 4.7 microM) [15].

Anatomical context of FR139317

• FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs [16].
• ETA and ETB receptors mediate contraction to endothelin-1 in renal artery of aging SHR. Effects of FR139317 and bosentan [17].
• We studied the effects of the selective endothelin A receptor antagonist FR139317 and the combined endothelin A/endothelin B receptor antagonist bosentan in rat mesenteric arteries by using a video dimension analyzer [18].
• Increase in the number of microglia/macrophages by a stab wound injury, which was determined by Griffonia simplicifolia isolectin B4 staining, was not affected by BQ788 and FR139317 [19].
• In addition, this study examined whether FR 139317 reduced infarct size in a rabbit model of coronary artery occlusion and reperfusion [20].

Associations of FR139317 with other chemical compounds

• Incubation of arteries from hypercholesterolemic pigs with BQ-788 (ETB-receptor antagonist), but not FR-139317 (ETA-receptor antagonist), altered the contractile response to ET-1 at 10(-10) mol/L [21].
• L-NAME (0.46 to 7.42 micromol/kg [0.125 to 2 mg/kg]) induced a dose-dependent increase in blood pressure, which was attenuated by 60% and 48% with bosentan and FR 139317, respectively (P<.01) [22].
• Cyclosporine (25 mg/kg per day) given for 4 weeks increased blood pressure from 98 +/- 12 to 156 +/- 14 mm Hg; this increase was blunted by coadministration of 10 mg/kg per day FR 139317 (ie, blood pressure was 138 +/- 14 mm Hg) in Wistar-Kyoto rats [23].
• Blood pressure, urinary protein excretion and serum creatinine were evaluated at days 0, 7 (before FR139317 or saline administration), 30, 45 and 60 [24].
• The ETA receptor-selective antagonists BQ-123 and FR139317 caused concentration-dependent inhibition of the contractions induced by endothelin-1 and sarafotoxin S6b, but both antagonists were significantly less potent in inhibiting contractions induced by endothelin-1 than sarafotoxin S6b [25].

Gene context of FR139317

• Moreover, the ETB receptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317 [26].
• In addition, the ET(A)-selective antagonist FR139317 inhibited ET-1-induced leptin expression more potently than did the ET(B)-selective antagonist BQ788 [27].
• In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied [3].
• Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, an endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin-B receptor agonist [28].
• 6. The results show that the ETA antagonists, BQ123 and FR139317, are highly selective for ETA receptors in all cardiac tissues tested, whereas BQ788 has a low affinity and no selectivity in this human tissue [29].

Analytical, diagnostic and therapeutic context of FR139317

• Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group) [2].
• In contrast, after organ culture the S6c-induced concentration-response curves were shifted parallel to the right in the following potency order: IRL 2500 > bosentan > FR139317 [30].
• The ETA receptor selective antagonists, BQ-123 and FR 139317, both partially blocked the increase in perfusion pressure induced by ET-1 [31].
• The effects of the endothelin ETA receptor antagonist, FR 139317, on infarct size in a rabbit model of acute myocardial ischaemia and reperfusion [20].
• 2. Intravenous injection of a selective ETA receptor antagonist, FR139317 (0.5 mumol kg-1, for 20 min) induced a very small fall in blood pressure [32].

References