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Vasoconstrictor effect of endothelin-1 in human skin: role of ETA and ETB receptors.
Am J Physiol. 1999 02; 276(2):H359-67.AJ

Abstract

The aim of this project was to investigate the role of ETA and ETB receptors in the mediation of endothelin (ET)-1-induced vasoconstriction in human skin. This information should provide important insights into the design of pharmacological intervention against skin vasospasm induced by ET-1 in peripheral vascular disease or surgical trauma. Vasoconstriction in response to intra-arterial drug infusion in isolated perfused human skin flaps (8 x 18 cm) derived from dermolipectomy specimens was assessed by studying changes in skin perfusion and perfusion pressure under constant flow rate in each drug treatment (n = 4). It was observed that ET-1 (10(-10) to 10(-8) M) and norepinephrine (NE, 10(-8) to 10(-5) M) caused skin vasoconstriction in a concentration-dependent manner, with the vasoconstrictor potency of ET-1 approximately 200-fold higher than NE. The ETA-receptor antagonist BQ-123 but not the ETB-receptor antagonist BQ-788 blocked the vasoconstrictor effect of ET-1. This observation was confirmed by studying skin perfusion using the dermofluorometry technique. In addition, ETB-receptor agonists BQ-3020 and sarafotoxin S6c (10(-9) to 10(-6) M) did not evoke skin vasoconstriction. BQ-3020 also did not elicit skin vasoconstriction even in the presence of 10(-5) M of Nomega-nitro-L-arginine methyl ester and indomethacin. Furthermore, results from saturable and competitive ET-1 radioligand membrane receptor binding assays revealed that high-affinity and capacity binding sites are predominantly the ETA receptor subtype in endothelium-denuded skin arteries and veins of 0.5-1.5 mm diameter, with an ETA-to-ETB receptor ratio of 83:17 in arteries (n = 5) and 78:22 in veins (n = 7). Results from the present functional and radioligand receptor binding studies clearly indicate that ET-1 is a very potent vasoconstrictor in human skin and its vasoconstrictor effect is primarily mediated by ETA receptors, with no significant participation from ETB receptors.

Authors+Show Affiliations

Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, H3H 1P3 Canada.No affiliation info availableNo affiliation info availableNo 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

9950834

Citation

Lipa, J E., et al. "Vasoconstrictor Effect of Endothelin-1 in Human Skin: Role of ETA and ETB Receptors." The American Journal of Physiology, vol. 276, no. 2, 1999, pp. H359-67.
Lipa JE, Neligan PC, Perreault TM, et al. Vasoconstrictor effect of endothelin-1 in human skin: role of ETA and ETB receptors. Am J Physiol. 1999;276(2):H359-67.
Lipa, J. E., Neligan, P. C., Perreault, T. M., Baribeau, J., Levine, R. H., Knowlton, R. J., & Pang, C. Y. (1999). Vasoconstrictor effect of endothelin-1 in human skin: role of ETA and ETB receptors. The American Journal of Physiology, 276(2), H359-67. https://doi.org/10.1152/ajpheart.1999.276.2.H359
Lipa JE, et al. Vasoconstrictor Effect of Endothelin-1 in Human Skin: Role of ETA and ETB Receptors. Am J Physiol. 1999;276(2):H359-67. PubMed PMID: 9950834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vasoconstrictor effect of endothelin-1 in human skin: role of ETA and ETB receptors. AU - Lipa,J E, AU - Neligan,P C, AU - Perreault,T M, AU - Baribeau,J, AU - Levine,R H, AU - Knowlton,R J, AU - Pang,C Y, PY - 1999/2/10/pubmed PY - 1999/2/10/medline PY - 1999/2/10/entrez SP - H359 EP - 67 JF - The American journal of physiology JO - Am J Physiol VL - 276 IS - 2 N2 - The aim of this project was to investigate the role of ETA and ETB receptors in the mediation of endothelin (ET)-1-induced vasoconstriction in human skin. This information should provide important insights into the design of pharmacological intervention against skin vasospasm induced by ET-1 in peripheral vascular disease or surgical trauma. Vasoconstriction in response to intra-arterial drug infusion in isolated perfused human skin flaps (8 x 18 cm) derived from dermolipectomy specimens was assessed by studying changes in skin perfusion and perfusion pressure under constant flow rate in each drug treatment (n = 4). It was observed that ET-1 (10(-10) to 10(-8) M) and norepinephrine (NE, 10(-8) to 10(-5) M) caused skin vasoconstriction in a concentration-dependent manner, with the vasoconstrictor potency of ET-1 approximately 200-fold higher than NE. The ETA-receptor antagonist BQ-123 but not the ETB-receptor antagonist BQ-788 blocked the vasoconstrictor effect of ET-1. This observation was confirmed by studying skin perfusion using the dermofluorometry technique. In addition, ETB-receptor agonists BQ-3020 and sarafotoxin S6c (10(-9) to 10(-6) M) did not evoke skin vasoconstriction. BQ-3020 also did not elicit skin vasoconstriction even in the presence of 10(-5) M of Nomega-nitro-L-arginine methyl ester and indomethacin. Furthermore, results from saturable and competitive ET-1 radioligand membrane receptor binding assays revealed that high-affinity and capacity binding sites are predominantly the ETA receptor subtype in endothelium-denuded skin arteries and veins of 0.5-1.5 mm diameter, with an ETA-to-ETB receptor ratio of 83:17 in arteries (n = 5) and 78:22 in veins (n = 7). Results from the present functional and radioligand receptor binding studies clearly indicate that ET-1 is a very potent vasoconstrictor in human skin and its vasoconstrictor effect is primarily mediated by ETA receptors, with no significant participation from ETB receptors. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9950834/Vasoconstrictor_effect_of_endothelin_1_in_human_skin:_role_of_ETA_and_ETB_receptors_ DB - PRIME DP - Unbound Medicine ER -