Endothelin-1 expression in hearts of transgenic hypertensive mice overexpressing angiotensin II

Shinichi Maki, Takashi Miyauchi, Satoshi Sakai, Tsutomu Kobayashi, Seiji Maeda, Yoshiko Takata, Fumihiro Sugiyama, Akiyoshi Fukamizu, Kazuo Murakami, Katsutoshi Goto, Yasuro Sugishita

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which has potent hypertrophic effects on cardiac myocytes. Although in cultured cardiomyocytes, angiotensin II (Ang II) was reported to enhance ET-1 production in vitro, it is not known whether ET-1 production is enhanced by Ang II in vivo. We investigated the production and pathophysiologic roles of ET-1 in 20-week-old male transgenic hypertensive mice (THM), in which the renin-angiotensin system (RAS) was markedly activated because of the presence of both human renin and angiotensinogen genes. Systolic blood pressure and the ratio of left ventricular weight to body weight were significantly higher in the THM than in control mice, indicating that THM developed cardiac hypertrophy. ET-1 production was significantly increased in the heart of THM because both ET-1 mRNA expression and peptide levels were significantly higher than in controls. However, circulating plasma ET-1 levels did not differ between the groups, and blood pressure did not change after i.v. injection with a high dose (3 mg/kg) of the ETA/B-nonselective receptor antagonist SB209670. These findings suggest that increased cardiac ET-1 production may contribute to the progression of cardiac hypertrophy and that endogenous ET-1 may not be involved in the short-term modulation of blood pressure in THM of this age.

Original languageEnglish
Pages (from-to)S412-S416
JournalJournal of Cardiovascular Pharmacology
Volume31
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • Angiotensin II
  • Cardiac hypertrophy
  • Endothelin-1
  • Hypertension
  • Renin-angiotensin system
  • Transgenic mice

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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