File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Endothelin-1 Is Involved in Norepinephrine-Induced Ventricular Hypertrophy in Vivo Acute Effects of Bosentan, an Orally Active, Mixed Endothelin ETA and ETB Receptor Antagonist

TitleEndothelin-1 Is Involved in Norepinephrine-Induced Ventricular Hypertrophy in Vivo Acute Effects of Bosentan, an Orally Active, Mixed Endothelin ETA and ETB Receptor Antagonist
Authors
Issue Date1996
Citation
Circulation, 1996, v. 93 n. 11, p. 2068-2079 How to Cite?
AbstractBackground: Endothelin-1 (ET-1) has potent effects on cell growth and induces hypertrophy of cultured ventricular myocytes. Catecholamines increase expression of ET-1 mRNA by cultured myocytes. We investigated the role of endogenous ET-1 in catecholamine-induced hypertrophy in vivo by studying the effects of continuous norepinephrine infusion on physical and molecular markers of ventricular hypertrophy, ventricular and noncardiac expression of ET-1 mRNA, and the acute effects of bosentan, an orally active ETA and ETB receptor antagonist. Methods and Results: Seventy male Sprague-Dawley rats (175 to 200 g) were divided into four groups: (1) sham-operated rats, (2) norepinephrine-infused rats (600 μg·kg-1·h-1 by subcutaneous osmotic pump, up to 7 days), (3) sham-operated rats given bosentan, and (4) norepinephrine-infused rats given bosentan. Bosentan (100 mg/kg once daily) was administered by gavage for 6 days starting 1 day before operation. Norepinephrine caused increases in absolute ventricular weight and ratios of ventricular weight to body weight and ventricular RNA to protein. Ventricular expression of mRNAs for atrial natriuretic factor, skeletal α-actin, and β-myosin heavy chain, which in adult rat ventricle are indicators of hypertrophy, also increased. Ventricular expression of ET-1 mRNA was elevated in the norepinephrine group at 1,2, and 3 days. By 5 days, this had fallen to control levels. In lung, kidney, and skeletal muscle, norepinephrine did not significantly increase expression of ET-1 mRNA. Bosentan attenuated norepinephrine-induced increases in ventricular weight, ratio of RNA to protein, and expression of skeletal α-actin mRNA and β-myosin heavy chain mRNA at 5 days, but it did not attenuate increased ventricular expression of atrial natriuretic factor mRNA. Conclusions: These data suggest that endogenous ET-1 plays a direct role in mediating norepinephrine-induced ventricular hypertrophy in vivo.
Persistent Identifierhttp://hdl.handle.net/10722/195239
ISSN
2015 Impact Factor: 17.047
2015 SCImago Journal Rankings: 7.853
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKaddoura, S-
dc.contributor.authorFirth, JD-
dc.contributor.authorBoheler, KR-
dc.contributor.authorSugden, PH-
dc.contributor.authorPoole-Wilson, PA-
dc.date.accessioned2014-02-25T01:40:20Z-
dc.date.available2014-02-25T01:40:20Z-
dc.date.issued1996-
dc.identifier.citationCirculation, 1996, v. 93 n. 11, p. 2068-2079-
dc.identifier.issn0009-7322-
dc.identifier.urihttp://hdl.handle.net/10722/195239-
dc.description.abstractBackground: Endothelin-1 (ET-1) has potent effects on cell growth and induces hypertrophy of cultured ventricular myocytes. Catecholamines increase expression of ET-1 mRNA by cultured myocytes. We investigated the role of endogenous ET-1 in catecholamine-induced hypertrophy in vivo by studying the effects of continuous norepinephrine infusion on physical and molecular markers of ventricular hypertrophy, ventricular and noncardiac expression of ET-1 mRNA, and the acute effects of bosentan, an orally active ETA and ETB receptor antagonist. Methods and Results: Seventy male Sprague-Dawley rats (175 to 200 g) were divided into four groups: (1) sham-operated rats, (2) norepinephrine-infused rats (600 μg·kg-1·h-1 by subcutaneous osmotic pump, up to 7 days), (3) sham-operated rats given bosentan, and (4) norepinephrine-infused rats given bosentan. Bosentan (100 mg/kg once daily) was administered by gavage for 6 days starting 1 day before operation. Norepinephrine caused increases in absolute ventricular weight and ratios of ventricular weight to body weight and ventricular RNA to protein. Ventricular expression of mRNAs for atrial natriuretic factor, skeletal α-actin, and β-myosin heavy chain, which in adult rat ventricle are indicators of hypertrophy, also increased. Ventricular expression of ET-1 mRNA was elevated in the norepinephrine group at 1,2, and 3 days. By 5 days, this had fallen to control levels. In lung, kidney, and skeletal muscle, norepinephrine did not significantly increase expression of ET-1 mRNA. Bosentan attenuated norepinephrine-induced increases in ventricular weight, ratio of RNA to protein, and expression of skeletal α-actin mRNA and β-myosin heavy chain mRNA at 5 days, but it did not attenuate increased ventricular expression of atrial natriuretic factor mRNA. Conclusions: These data suggest that endogenous ET-1 plays a direct role in mediating norepinephrine-induced ventricular hypertrophy in vivo.-
dc.languageeng-
dc.relation.ispartofCirculation-
dc.titleEndothelin-1 Is Involved in Norepinephrine-Induced Ventricular Hypertrophy in Vivo Acute Effects of Bosentan, an Orally Active, Mixed Endothelin ETA and ETB Receptor Antagonist-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid8640984-
dc.identifier.scopuseid_2-s2.0-0029886332-
dc.identifier.volume93-
dc.identifier.issue11-
dc.identifier.spage2068-
dc.identifier.epage2079-
dc.identifier.isiWOS:A1996UM92800021-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats