Pharmacologic Characterization of an EndothelinA (ETA) Receptor Antagonist in Conscious Rats

Bazil, Michelle K.; Lappe, Rodney W.; Webb, Randy L.

doi:10.1097/00005344-199212000-00014

Cited by 83 publications

(34 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The vasodilative effect of ET-1 is induced by the binding of ET-1 to the ETB receptor (15, 16). On the other hand, a highly selective ETA-receptor antagonist , ~cyclo[D-Asp-L-Pro-D-allo-Ile-L-Leu-DTrp] (BQ-123), isolated from Streptomyces misakiensis by Ihara et al (17), has been reported to inhibit the pressor response elicited by ET-1 in the rat (18). Moreover, BQ-123 inhibited the ET-1-mobilized [Ca2+ Ii concentration and the ET-1-induced synthesis of DNA (19)(20)(21).…”

mentioning

confidence: 99%

Inhibitory Effect of BQ-123 on Endothelin-1-Stimulated Mitogen-Activated Protein Kinase and Cell Growth of Rat Vascular Smooth Muscle Cells.

Okada

Fujita

et al. 1996

Hypertens Res

View full text Add to dashboard Cite

Studies have suggested that endothelin-1 (ET-1) activates cellular contraction and proliferation in rat vascular smooth muscle cells (VSMC). We examined whether an ETA receptor antagonist, BQ-123, inhibits the following cellular actions of ET-1 in rat VSMC: cytosolic free calcium ([Ca2+] with BQ-123 did not enhance its inhibitory effects but these effects of BQ-123 were diminished by washing after preincubation. Receptor studies revealed that the washing procedure decreased the inhibitory effect of BQ-123 on ET-1 binding to receptors.These results indicate that BQ-123 is a potent and specific ETA receptor antagonist that blocks the ET-1-induced cellular contraction and proliferation in rat VSMC. (Hypertens Res 1996; 19: 23-30)

show abstract

mentioning

confidence: 99%

Inhibitory Effect of BQ-123 on Endothelin-1-Stimulated Mitogen-Activated Protein Kinase and Cell Growth of Rat Vascular Smooth Muscle Cells.

Okada

Fujita

et al. 1996

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…receptors are thought to be located on the vascular smooth muscle, and their mechanism of action is unknown (1 [2][3][4][5][6][7][8][9][10][11][12][13][14].…”

mentioning

confidence: 99%

The Role of Endothelin and Endothelin Receptor Subtypes in Regulation of Fetal Pulmonary Vascular Tone

1994

View full text Add to dashboard Cite

ABSTRACT. The physiologic role of endothelin-1 (ET-1) and its receptors in regulating fetal pulmonary vascular tone is unknown. We therefore investigated the role of ET-1 and its receptors in the regulation of fetal pulmonary vascular tone using BQ 123 (an ET, receptor antagonist) and 4 Ala ET-1 (an ETb receptor agonist). In six fetal sheep in utero, we found that injections of ET-1 (250 ng/ kg fetal weight) into the left pulmonary artery increased left pulmonary blood flow (21.0 f 17.5 to 74.7 f 32.9 mL/ kg/min, p < 0.05) and decreased left pulmonary vascular resistance (6.02 f 7.00 to 0.84 f 0.48 mm Hg/kg/min/mL, p c 0.05). BQ 123 (5 mg) increased pulmonary blood flow (24.6 f 28.7 to 47.7 f 27.4 mL/kg/min, p < 0.05) and 1 1, 18). We have previously shown that BQ 123 is a selective ET, antagonist in newborn lambs and inhibits ET-I-induced pulmonary vasoconstriction (8). In contrast to BQ 123,4 Ala ET-1 is a selective ETh agonist that induces pulmonary vasodilation during U44619-induced pulmonary hypertension ( 18).This study had two main objectives. The first was to investigate the role of ET-I and its receptors in the regulation of pulmonary vascular tone in near-term, chronically instrumented fetal sheep in tttero by studying the effects of a selective ET-I receptor antagonist and agonist. The second objective was to investigate the mechanism of the ET-I effect on the pulmonary circulation. For the first objective, we studied the effects of injections of ET-1 and 4 Ala ET-I into the left pulmonary artery and inferior vena cava and infusions of BQ 123 into the left pulmonary artery on fetal pulmonary vascular tone. For the second objective, we compared the hemodynamic effects of exogenous ET-1 before and during the infusion of glibenclamide (an ATP-dependent potassium channel blocker). MATERIALS AND METHODSSztrgical preparation. Fetal surgery was performed as previously described (19). Briefly, a total of six Western fetal sheep were studied at 135.8 k 6.1 d gestational age (term 145 d). The ewe was anesthetized with an epidural injection of 4 mL of I % tetracaine hydrochloride. Polyvinyl catheters were inserted into the maternal pedal vein and artery after local infiltration with 2% lidocaine hydrochloride.With use of aseptic techniques, the uterus was exposed through a midline incision. Through a small uterine incision the hind limb was exposed, and polyvinyl catheters were inserted into the fetal wdal vein and artery and their tips advanced to the descend- Polyvinyl catheters were then inserted into the internal thoracic

show abstract

“…19 Bosentan is a recently developed, long-acting, nonselective endothelin receptor antagonist. It blocks both ET A and ET B receptors.…”

Section: Effects Of Bosentanmentioning

confidence: 99%

Endothelin Inhibition as a Biologic Target for Treating Hypertension

Brunner

1998

American Journal of Hypertension

View full text Add to dashboard Cite

Endothelin, a 21-amino-acid peptide, binds to a specific receptor on vascular smooth muscle cells, thereby inducing vasoconstriction. Although plasma levels are not consistently elevated in hypertension, there is evidence that endothelin has an important role in its pathogenesis. Administration of endothelin antagonists has lowered blood pressure and reduced end-organ damage in some animal models. It has also reduced the cross-sectional area of neointima due both to hypertension and vascular injury. T he endothelium plays a role in regulating vascular resistance by releasing substances that dilate or constrict blood vessels. These substances, endothelins, are a family of peptides having potent vasoconstrictive effects. There are basically three types of endothelin: endothelin-1, endothelin-2, and endothelin-3. They are all formed from precursors (big endothelin) by enzymatic cleavage and are all 21-amino-acid peptides with disulfide bridges (Figure 1). Endothelin-1 and endothelin-2 act on the endothelin-A (ET A ) receptor of smooth muscle to produce a prolonged contraction and vasoconstriction. Endothelin-3 can also induce vasoconstriction by binding to the endothelin-B (ET B ) receptor on smooth muscle, but it also acts on the ET B receptors of endothelial cells, where it can actually have the opposite effect. It has been suggested that, under normal conditions, low concentrations of endothelin stimulate ET B receptors, thus contributing to the release of endothelium-derived relaxing factors. 1 Endothelin-1 is probably the best studied of this family. When administered to animals, endothelin-1 causes severe vasoconstriction. 2 The contraction of vascular smooth muscle produced by endothelin-1 may be mediated by an increase in intracellular calcium, but the details have not been established. 3 Infusion of endothelin-1 into healthy human volunteers resulted in a 2.5-fold increase in plasma endothelin-1 concentration and a rise

show abstract

Pharmacologic Characterization of an EndothelinA (ETA) Receptor Antagonist in Conscious Rats

Cited by 83 publications

References 0 publications

Inhibitory Effect of BQ-123 on Endothelin-1-Stimulated Mitogen-Activated Protein Kinase and Cell Growth of Rat Vascular Smooth Muscle Cells.

Inhibitory Effect of BQ-123 on Endothelin-1-Stimulated Mitogen-Activated Protein Kinase and Cell Growth of Rat Vascular Smooth Muscle Cells.

The Role of Endothelin and Endothelin Receptor Subtypes in Regulation of Fetal Pulmonary Vascular Tone

Endothelin Inhibition as a Biologic Target for Treating Hypertension

Contact Info

Product

Resources

About