3 years ago

Obligatory Metabolism of Angiotensin II to Angiotensin III for Zona Glomerulosa Cell-Mediated Relaxations of Bovine Adrenal Cortical Arteries.

Phillip G Kopf, Sang-Kyu Park, William B Campbell, Bernard P Roques, Christian Krause, Anja Herrnreiter
Hyperaldosteronism is associated with hypertension, cardiac hypertrophy, and congestive heart failure. Steroidogenic factors facilitate aldosterone secretion by increasing adrenal blood flow. Angiotensin II (Ang II) decreases adrenal vascular tone through release of zona glomerulosa (ZG) cell-derived vasodilatory eicosanoids. However, ZG cell-mediated relaxations of bovine adrenal cortical arteries to Ang II are not altered by AT1 or AT2 receptor antagonists. Since traditional Ang II receptors do not mediate these vasorelaxations to Ang II, we investigated the role of Ang II metabolites. Ang III was identified by LC/MS as the primary ZG cell metabolite of Ang II. Ang III stimulated ZG cell-mediated relaxations of adrenal arteries with greater potency than Ang II. Furthermore, ZG cell-mediated relaxations of adrenal arteries by Ang II are attenuated by aminopeptidase inhibition, while Ang III-stimulated relaxations persisted. Ang IV had little effect as compared to Ang II. Moreover, ZG cell-mediated relaxations of adrenal arteries by Ang II were attenuated by an Ang III antagonist, but not by an Ang (1-7) antagonist. In contrast, Ang II and Ang III were equipotent in stimulating aldosterone secretion from ZG cells and were unaffected by aminopeptidase inhibition. Additionally, aspartyl- and leucyl-aminopeptidases, that convert Ang II to Ang III, are the primary peptidase expressed in ZG cells. This was confirmed by enzyme activity. These data indicate that intra-adrenal metabolism of Ang II to Ang III is required for ZG cell-mediated relaxations of adrenal arteries but not aldosterone secretion. These studies define an important new role of Ang III in the adrenal gland.

Publisher URL: http://doi.org/10.1210/en.2017-00759

DOI: 10.1210/en.2017-00759

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.