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Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels.
Circulation. 1994 Mar; 89(3):1203-8.Circ

Abstract

BACKGROUND

Endothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ETA receptor, which preferentially binds ET-1, and the ETB receptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein (IMV) and porcine coronary artery (PCA) using the ETA antagonists FR139317 and BQ-123, the ETB ligand sarafotoxin S6c, and the ETA/ETB antagonist Ro 47-0203 (bosentan).

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. However, even at 10(-5) mol/L, FR139317 did not inhibit a high-sensitivity portion of the concentration-contraction curve. Moreover, the ETB receptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317. IMV was significantly more sensitive to the contractile effect of ET-1 and sarafotoxin S6c than was IMA (P < .05). Prolonged incubation with sarafotoxin S6c (to downregulate ETB receptors) and FR139317 eliminated the contraction resistant to FR139317. The ETA/ETB receptor antagonist bosentan caused a parallel shift of the concentration-contraction curve to the right at all concentrations of endothelin. ETB receptor mRNA was detected by Northern blot analysis in IMA and aortic smooth muscle cells. In precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause endothelium-dependent relaxations, whereas transient responses occurred in IMV.

CONCLUSIONS

Vascular smooth muscle cells of human IMA, IMV, and PCA contain both ETA and ETB receptors, whereas the endothelium of IMA and PCA does not express functional ETB receptors linked to nitric oxide and/or prostacyclin production. Hence, inhibition of endothelin-induced contraction in patients requires the use of combined ETA/ETB antagonists.

Authors+Show Affiliations

Department of Research, University Hospitals, Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8124808

Citation

Seo, B, et al. "Both ETA and ETB Receptors Mediate Contraction to Endothelin-1 in Human Blood Vessels." Circulation, vol. 89, no. 3, 1994, pp. 1203-8.
Seo B, Oemar BS, Siebenmann R, et al. Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation. 1994;89(3):1203-8.
Seo, B., Oemar, B. S., Siebenmann, R., von Segesser, L., & Lüscher, T. F. (1994). Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation, 89(3), 1203-8.
Seo B, et al. Both ETA and ETB Receptors Mediate Contraction to Endothelin-1 in Human Blood Vessels. Circulation. 1994;89(3):1203-8. PubMed PMID: 8124808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. AU - Seo,B, AU - Oemar,B S, AU - Siebenmann,R, AU - von Segesser,L, AU - Lüscher,T F, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 1203 EP - 8 JF - Circulation JO - Circulation VL - 89 IS - 3 N2 - BACKGROUND: Endothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ETA receptor, which preferentially binds ET-1, and the ETB receptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein (IMV) and porcine coronary artery (PCA) using the ETA antagonists FR139317 and BQ-123, the ETB ligand sarafotoxin S6c, and the ETA/ETB antagonist Ro 47-0203 (bosentan). 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. However, even at 10(-5) mol/L, FR139317 did not inhibit a high-sensitivity portion of the concentration-contraction curve. Moreover, the ETB receptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317. IMV was significantly more sensitive to the contractile effect of ET-1 and sarafotoxin S6c than was IMA (P < .05). Prolonged incubation with sarafotoxin S6c (to downregulate ETB receptors) and FR139317 eliminated the contraction resistant to FR139317. The ETA/ETB receptor antagonist bosentan caused a parallel shift of the concentration-contraction curve to the right at all concentrations of endothelin. ETB receptor mRNA was detected by Northern blot analysis in IMA and aortic smooth muscle cells. In precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause endothelium-dependent relaxations, whereas transient responses occurred in IMV. CONCLUSIONS: Vascular smooth muscle cells of human IMA, IMV, and PCA contain both ETA and ETB receptors, whereas the endothelium of IMA and PCA does not express functional ETB receptors linked to nitric oxide and/or prostacyclin production. Hence, inhibition of endothelin-induced contraction in patients requires the use of combined ETA/ETB antagonists. SN - 0009-7322 UR - https://www.unboundmedicine.com/medline/citation/8124808/Both_ETA_and_ETB_receptors_mediate_contraction_to_endothelin_1_in_human_blood_vessels_ L2 - https://www.ahajournals.org/doi/10.1161/01.cir.89.3.1203?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -