| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pharmacology, University of Sherbrooke, Sherbrooke, Quebec, Canada
2 Anatomy and Cell biology, University of Sherbrooke, Sherbrooke, Quebec, Canada
* To whom correspondence should be addressed. E-mail: labpdj{at}usherbrooke.ca.
In the vascular system, endothelin (ET) B receptors for ET-1 are located on endothelial and on venous and arterial smooth muscle cells. In the present study, we investigated the hemodynamic effects afforded by chronic ETB receptor blockade at low and high doses, in the Syrian Golden hamster. After 16 days of gavage with A-192621, a selective ETB antagonist, at 0.5 or 30 mg/kg/d, hamsters were anesthetized with ketamine/xylazine (87/13 mg/kg, i.m.) and basal mean arterial blood pressure (MAP), as well as pressor responses to exogenous ET-1, were evaluated. We observed that the lower dose of A-192621 (0.5 mg/kg/d) did not modify basal MAP, while the higher dose (30 mg/kg/d) increased MAP and ET plasma levels. Radio-telemetric recordings confirmed the increase of MAP afforded by the higher dose of A-192621, in conscious hamsters. On the other hand, the lower dose of A-192621, although devoid of intrinsic pressor effects, markedly reduced the transient hypotensive phase induced by intravenously-injected IRL-1620, a selective ETB receptor agonist. Finally, A-192621 (0.5 mg/kg/d) alone, or A-192621 (30 mg/kg/d) plus atrasentan (6 mg/kg/d), a selective ETA antagonist, potentiated the pressor response to exogenous ET-1. Our results suggest that in the hamster, ETB receptors located on vascular smooth muscle cells are importantly involved in the clearance of endogenous ET-1 whereas the same receptor type on the endothelium is solely involved in the vasodilatory responses to the pressor peptide. Blockade of both endothelial and vascular smooth muscle cell ETB receptors triggers a marked potentiation of ETA-dependent increases in systemic resistance.
This article has been cited by other articles:
|
|
 |
|
  K. Sachidanandam, M. M. Elgebaly, A. K. Harris, J. R. Hutchinson, E. M. Mezzetti, V. Portik-Dobos, and A. Ergul Effect of chronic and selective endothelin receptor antagonism on microvascular function in Type 2 diabetes Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2743 - H2749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Linder, J. Diaz, W. Ni, T. Szasz, R. Burnett, and S. W. Watts Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1745 - H1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Abassi, B. Bishara, T. Karram, S. Khatib, J. Winaver, and A. Hoffman Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R842 - R850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fink, M. Li, Y. Lau, J. Osborn, and S. Watts Chronic Activation of Endothelin B Receptors: New Model of Experimental Hypertension Hypertension, September 1, 2007; 50(3): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
