Regulation of the myocardial endothelin system by angiotensin-II and losartan

P. E. McEwan*, L. Sherry, C. J. Kenyon, D. J. Webb, G. A. Gray

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Evidence for interactions between the endothelin (ET) and renin-angiotensin systems is plentiful in vitro, but few studies have investigated these interactions in vivo. In the study reported here, we have investigated the influence of chronic angiotensin-II (A-II) infusion in vivo on expression of preproendothelin-1 (PPET-1) and endothelin-A- (ET(A)) and endothelin-B- (ET(B)) receptor mRNA in the heart. The role of the angiotensin type 1 (AT1)-receptor in mediating the actions of A-II was studied using losartan, the selective AT1-receptor antagonist. Male rats received an infusion of A-II (200 ng/kg/min) or vehicle for 14 days via mini-osmotic pumps; losartan (10 mg/kg/day) was administered in the drinking water. PPET-1 and ET(A)- and ET(B)-receptor mRNA were detected in heart sections using nonradioactive antisense in situ hybridization. Independent treatments with either A-II or losartan had no significant effect on PPET-1, ET(A)- or ET(B)-receptor expression. Combined treatment resulted in an increase in PPET-1 mRNA (p < 0.001) and ET(B)-receptor mRNA expression (p < 0.01), while ET(A)-receptor mRNA expression was decreased (p < 0.001). These results suggest that selective AT1-receptor blockade, in the presence of an elevated plasma A-II concentration, causes upregulation of ET-1 synthesis in the myocardium as well as modification of ET receptor expression. These effects may be mediated via angiotensin type 2 (AT2)-receptors.

Original languageEnglish
Pages (from-to)S144-S147
JournalJournal of cardiovascular pharmacology
Issue number5 SUPPL. 1
Publication statusPublished - 1 Nov 2000

Keywords / Materials (for Non-textual outputs)

  • Angiotensin-II (A-II)
  • AT1-receptor antagonist
  • Endothelin (ET)
  • ET(A)-receptor
  • ET(B)-receptor
  • Myocardium


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