The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

Webb, Maria L.; Dickinson, Kenneth E.J.; Delaney, Carol; Liu, Eddie C.‐K.; Serafino, Randy; Cohen, Robert B.; Monshizadegan, Hossain; Moreland, Suzanne

doi:10.1016/0006-291x(92)91710-8

Cited by 54 publications

(25 citation statements)

References 20 publications

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“…Human ET A affinity studies were performed as described previously (Webb et al, 1992). Stably transfected CHO-K1 cells expressing either the human endothelin A or endothelin B receptors were cultured in Ham's F-12 media (Invitrogen) with 10% fetal bovine serum (Hyclone Laboratories, Logan, UT), supplemented with 300 g/ml Geneticin (G-418; Invitrogen) and maintained at 37°C with 5% CO 2 in a humidified incubator.…”

Section: Radioligand Binding Studiesmentioning

confidence: 99%

“…Conversely, ET-1 treatment of pulmonary endothelial cells stimulates the conversion of Ang I to Ang II (Kawaguchi et al, 1990). BQ-123 (a peptidic ET A receptor antagonist) shifted the Ang II-mediated contraction response curves of rabbit aortas to the right (Webb et al, 1992), and ET A receptor antagonism inhibits vasoconstriction due to Ang II (Wenzel et al, 2001). The interaction between Ang II and ET-1 is further exemplified by the fact that low doses of either Ang II or ET-1 infused into rats had no effect on blood pressure, but simultaneous infusion of low doses of both peptides increased blood pressure dramatically (Yoshida et al, 1992).…”

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confidence: 99%

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Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Kowala¹,

Murugesan²,

Tellew³

et al. 2004

J Pharmacol Exp Ther

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Angiotensin II and endothelin-1 activate their respective AT 1 and ET A receptors on vascular smooth muscle cells, producing vasoconstriction, and both peptides are implicated in the pathogenesis of essential hypertension. Angiotensin II potentiates the production of endothelin, and conversely endothelin augments the synthesis of angiotensin II. Both AT 1 and ET A receptor antagonists lower blood pressure in hypertensive patients; thus, a combination AT 1 /ET A receptor antagonist may have greater efficacy and broader utility compared with each drug alone. By rational drug design a biphenyl ET A receptor blocker was modified to acquire AT 1 receptor antagonism. These compounds (C and D) decreased Sar-Ile-Angiotensin II binding to AT 1 receptors and endothelin-1 binding to ET A receptors, and compound C inhibited angiotensin II-and endothelin-1-mediated Ca 2ϩ transients. In rats compounds C and D reduced blood pressure elevations caused by intravenous infusion of angiotensin II or big endothelin-1. Compound C decreased blood pressure in Na ϩ -depleted spontaneously hypertensive rats and in rats with mineralocorticoid hypertension. Compound D was more efficacious than AT 1 receptor antagonists at reducing blood pressure in spontaneously hypertensive rats, and its superiority was likely due to its partial blockade of ET A receptors. Therefore compounds C and D are novel agents for treating a broad spectrum of patients with essential hypertension and other cardiovascular diseases.

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Section: Radioligand Binding Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Kowala¹,

Murugesan²,

Tellew³

et al. 2004

J Pharmacol Exp Ther

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“…Threshold concentrations of endothelin have been shown to sensitize vascular smooth muscle to, for example, norepinephrine and serotonin [10,67]. In line with these findings, Webb et al [74] have demonstrated in rabbit aorta that angiotensin II induced contractions can be inhibited with an endothelin receptor antagonist (BQ123).…”

Section: In Vitro Studiesmentioning

confidence: 78%

Role of endothelin in hypertension

et al. 1994

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“…It has been suggested that an interaction exists between the renin-angiotensin system and the endothelin system, and that angiotensin II stimulates the release of endothelin from bovine endothelial cells, porcine aortic strips, and resistance vessels in the mesenteric vascular bed of the rat (Bakris and Re 1993;Chen et al 1995aChen et al , 1995bDohi et al 1992;Imai et al 1992;Webb et al 1992). More recently, it has been reported that the nonpeptide ET A /ET B receptor antagonist bosentan inhibits pressor responses to intravenous injection of low doses of angiotensin II but does not alter pressor responses to higher doses of the peptide in the spontaneously hypertensive and normotensive rat (Balakrishnan et al 1996).…”

Section: Figmentioning

confidence: 98%

Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ET_A/ET_B receptor antagonist, in the hind-limb vascular bed of the cat

Champion¹,

Estrada²,

Estrada³

et al. 1998

Can. J. Physiol. Pharmacol.

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The effects of bosentan (Ro 47-0203), an endothelin A and B receptor antagonist, on responses to endothelin-1, sarafotoxin 6c, angiotensin II, and arginine vasopressin were investigated in the hind-limb vascular bed of the cat. Under constant-flow conditions, intraarterial injections of endothelin-1 and sarafotoxin 6c induced biphasic changes in hind-limb perfusion pressure characterized by an initial decrease followed by a secondary increase in perfusion pressure. The vasodilator and vasoconstrictor components of the biphasic responses to endothelin-1 and sarafotoxin 6c were reduced by bosentan, and the endothelin receptor antagonist reduced baseline systemic arterial and hind-limb perfusion pressures. Bosentan decreased vasoconstrictor responses to lower doses of angiotensin II, whereas responses to higher doses of angiotensin II and responses to vasopressin, U46619, BAY K8644, norepinephrine, acetylcholine, bradykinin, levcromakalim, PGE1, adrenomedullin, and calcitonin gene-related peptide were not altered. Vasoconstrictor responses to ET-1 were not altered by the angiotensin AT1 receptor antagonist DuP 532 or the AT2 receptor antagonist PD123,319. The results of the present study show that bosentan attenuates vasodilator and vasoconstrictor responses to endothelin-1 and sarafotoxin 6c and vasoconstrictor responses to lower doses of angiotensin II in the hind-limb vascular bed of the cat. These results suggest that endothelin may be involved in mediating responses to lower doses of angiotensin II and in the maintenance of baseline tone in the systemic vascular bed of the cat.

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The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

Cited by 54 publications

References 20 publications

Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Role of endothelin in hypertension

Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ET_A/ET_B receptor antagonist, in the hind-limb vascular bed of the cat

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The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

Cited by 54 publications

References 20 publications

Novel Dual Action AT1 and ETA Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Novel Dual Action AT1 and ETA Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Role of endothelin in hypertension

Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ETA/ETB receptor antagonist, in the hind-limb vascular bed of the cat

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Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Novel Dual Action AT₁ and ET_A Receptor Antagonists Reduce Blood Pressure in Experimental Hypertension

Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ET_A/ET_B receptor antagonist, in the hind-limb vascular bed of the cat