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Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats.
Br J Pharmacol. 1995 Aug; 115(8):1377-81.BJ

Abstract

1. Endothelin-1 gene expression is enhanced in aorta and mesenteric arteries, and possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt hypertensive rats but is normal or reduced in spontaneously hypertensive rats (SHR). Bosentan, a mixed ETA/ETB endothelin receptor antagonist, blunts the development of elevated blood pressure of DOCA-salt hypertensive rats but not in SHR. In this study we investigated whether treatment of DOCA-salt SHR with bosentan would result in blunted rise in blood pressure. 2. SHR, aged 13 weeks, were implanted with silastic containing DOCA and offered 1% saline to drink. Systolic blood pressure was measured by the tail-cuff method. Endothelin-1 mRNA abundance in aorta and mesenteric arteries was measured by Northern blot analysis. Content of immunoreactive endothelin in blood vessels was measured by radioimmunoassay. 3. Systolic blood pressure rose less in bosentan-treated DOCA-salt SHR (to 223 +/- 2 mmHg) in comparison to the untreated rats (241 +/- 1), a small but significant difference (P < 0.001). However, blood pressure of bosentan-treated DOCA-salt SHR was still higher than in age-matched SHR. Endothelin-1 mRNA abundance and content of immunoreactive endothelin were increased in the aorta and the mesenteric arterial bed of DOCA-salt SHR, and were unaffected by treatment with bosentan. 4. These data support the hypothesis of a role of endothelin-1 in blood pressure elevation in this hypertensive model with malignant hypertension. They also support the hypothesis that an antihypertensive effect of the mixed ETA/ETB endothelin receptor antagonist, bosentan, is found when experimental hypertensive animals exhibit enhanced endothelin-1 gene expression in blood vessels.

Authors+Show Affiliations

MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.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

8564194

Citation

Schiffrin, E L., et al. "Antihypertensive Effect of an Endothelin Receptor Antagonist in DOCA-salt Spontaneously Hypertensive Rats." British Journal of Pharmacology, vol. 115, no. 8, 1995, pp. 1377-81.
Schiffrin EL, Sventek P, Li JS, et al. Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats. Br J Pharmacol. 1995;115(8):1377-81.
Schiffrin, E. L., Sventek, P., Li, J. S., Turgeon, A., & Reudelhuber, T. (1995). Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats. British Journal of Pharmacology, 115(8), 1377-81.
Schiffrin EL, et al. Antihypertensive Effect of an Endothelin Receptor Antagonist in DOCA-salt Spontaneously Hypertensive Rats. Br J Pharmacol. 1995;115(8):1377-81. PubMed PMID: 8564194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats. AU - Schiffrin,E L, AU - Sventek,P, AU - Li,J S, AU - Turgeon,A, AU - Reudelhuber,T, PY - 1995/8/1/pubmed PY - 1995/8/1/medline PY - 1995/8/1/entrez SP - 1377 EP - 81 JF - British journal of pharmacology JO - Br J Pharmacol VL - 115 IS - 8 N2 - 1. Endothelin-1 gene expression is enhanced in aorta and mesenteric arteries, and possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt hypertensive rats but is normal or reduced in spontaneously hypertensive rats (SHR). Bosentan, a mixed ETA/ETB endothelin receptor antagonist, blunts the development of elevated blood pressure of DOCA-salt hypertensive rats but not in SHR. In this study we investigated whether treatment of DOCA-salt SHR with bosentan would result in blunted rise in blood pressure. 2. SHR, aged 13 weeks, were implanted with silastic containing DOCA and offered 1% saline to drink. Systolic blood pressure was measured by the tail-cuff method. Endothelin-1 mRNA abundance in aorta and mesenteric arteries was measured by Northern blot analysis. Content of immunoreactive endothelin in blood vessels was measured by radioimmunoassay. 3. Systolic blood pressure rose less in bosentan-treated DOCA-salt SHR (to 223 +/- 2 mmHg) in comparison to the untreated rats (241 +/- 1), a small but significant difference (P < 0.001). However, blood pressure of bosentan-treated DOCA-salt SHR was still higher than in age-matched SHR. Endothelin-1 mRNA abundance and content of immunoreactive endothelin were increased in the aorta and the mesenteric arterial bed of DOCA-salt SHR, and were unaffected by treatment with bosentan. 4. These data support the hypothesis of a role of endothelin-1 in blood pressure elevation in this hypertensive model with malignant hypertension. They also support the hypothesis that an antihypertensive effect of the mixed ETA/ETB endothelin receptor antagonist, bosentan, is found when experimental hypertensive animals exhibit enhanced endothelin-1 gene expression in blood vessels. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/8564194/Antihypertensive_effect_of_an_endothelin_receptor_antagonist_in_DOCA_salt_spontaneously_hypertensive_rats_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0007-1188&amp;date=1995&amp;volume=115&amp;issue=8&amp;spage=1377 DB - PRIME DP - Unbound Medicine ER -