This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wenzel, R. R. Articles by Luscher, T. F. Search for Related Content PubMed PubMed Citation Articles by Wenzel, R. R. Articles by Luscher, T. F.

Hypertension, Vol 23, 581-586, Copyright © 1994 by American Heart Association

ARTICLES

Endothelin receptor antagonists inhibit endothelin in human skin microcirculation

RR Wenzel, G Noll and TF Luscher
Division of Cardiology, University Hospital, Inselspital, Bern, Switzerland.

Endothelin is a potent vasoconstrictor peptide produced by endothelial cells, but its role in physiology and disease is uncertain. We investigated the influence of the endothelin-A-selective receptor antagonist PD 147953 and the nonselective endothelin receptor antagonist PD 145065 on the effects of endothelin-1 and endothelin-3 in the skin microcirculation of healthy volunteers, using laser Doppler flowmetry. A double injection model was developed, allowing simultaneous injection of two substances, ie, agonist and antagonist or saline. The injection of saline led to a well-defined vasodilation at the injection site (maximum increase, from 19 +/- 2 to 97 +/- 15 perfusion units at 6 minutes; P < .001; n = 10). Endothelin-1 (10(-12) mol) decreased blood flow (difference from saline control, -79 +/- 14 perfusion units; P < .001; n = 11) within the injection wheal (diameter, 4 to 5 mm), while endothelin-3 had no effect. In the surrounding area (at 8 mm from the injection site), both endothelin-1 (+116 +/- 32 perfusion units; P < .001; n = 11) and endothelin-3 (+59 +/- 16 perfusion units; P < .001; n = 11) markedly increased blood flow. Both endothelin receptor antagonists slightly increased blood flow (maximum difference from control, +56 +/- 18 [PD 147953] and +31 +/- 10 [PD 145065] perfusion units; P < .05; n = 8) and inhibited endothelin-1-induced (P < .01) vasoconstriction. The vasoconstriction to norepinephrine was not affected by the endothelin antagonist PD 147953. Endothelin-1- and endothelin-3-induced vasodilation in the surrounding area were also inhibited by both endothelin antagonists or by lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				C. Binggeli, L. E. Spieker, R. Corti, I. Sudano, V. Stojanovic, D. Hayoz, T. F. Luscher, and G. Noll Statins enhance postischemic hyperemia in the skin circulation of hypercholesterolemic patients: A monitoring test of endothelial dysfunction for clinical practice? J. Am. Coll. Cardiol., July 2, 2003; 42(1): 71 - 77. [Abstract] [Full Text] [PDF]

				D. L. Kellogg Jr., Y. Liu, and P. E. Pergola Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans J Appl Physiol, November 1, 2001; 91(5): 2407 - 2411. [Abstract] [Full Text] [PDF]

				T. F. Luscher and M. Barton Endothelins and Endothelin Receptor Antagonists : Therapeutic Considerations for a Novel Class of Cardiovascular Drugs Circulation, November 7, 2000; 102(19): 2434 - 2440. [Abstract] [Full Text] [PDF]

				J. E. Lipa, P. C. Neligan, T. M. Perreault, J. Baribeau, R. H. Levine, R. J. Knowlton, and C. Y. Pang Vasoconstrictor effect of endothelin-1 in human skin: role of ETA and ETB receptors Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H359 - H367. [Abstract] [Full Text] [PDF]

				C. Cardillo, C. M. Kilcoyne, M. Waclawiw, R. O. Cannon III, and J. A. Panza Role of Endothelin in the Increased Vascular Tone of Patients With Essential Hypertension Hypertension, February 1, 1999; 33(2): 753 - 758. [Abstract] [Full Text] [PDF]

				R. R. Wenzel, M. Fleisch, S. Shaw, G. Noll, U. Kaufmann, R. Schmitt, C. R. Jones, M. Clozel, B. Meier, and T. F. Luscher Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease Circulation, November 24, 1998; 98(21): 2235 - 2240. [Abstract] [Full Text] [PDF]

				C. Y. Pang, J. Zhang, H. Xu, J. E. Lipa, C. R. Forrest, and P. C. Neligan Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1066 - R1074. [Abstract] [Full Text] [PDF]

				R. R. Wenzel, N. Duthiers, G. Noll, J. Bucher, U. Kaufmann, and T. F. Luscher Endothelin and Calcium Antagonists in the Skin Microcirculation of Patients With Coronary Artery Disease Circulation, August 1, 1996; 94(3): 316 - 322. [Abstract] [Full Text]

				W. G. Haynes, F. E. Strachan, and D. J. Webb Endothelin ETA and ETB Receptors Cause Vasoconstriction of Human Resistance and Capacitance Vessels In Vivo Circulation, August 1, 1995; 92(3): 357 - 363. [Abstract] [Full Text]

				E. L. Schiffrin Endothelin: Potential Role in Hypertension and Vascular Hypertrophy Hypertension, June 1, 1995; 25(6): 1135 - 1143. [Abstract] [Full Text]

				C. F. Kung and T. F. Luscher Different Mechanisms of Endothelial Dysfunction With Aging and Hypertension in Rat Aorta Hypertension, February 1, 1995; 25(2): 194 - 200. [Abstract] [Full Text]