Endothelin-1-independent and angiotensin II-independent induction of adrenomedullin gene expression

Hannu Romppanen, Jutta Puhakka, Gábor Földes, István Szokodi, Olli Vuolteenaho, Heikki Tokola, Miklós Tóth, Heikki Ruskoaho

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19 Citations (Scopus)

Abstract

Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the precise time course of induction of atrial and ventricular AM gene expression during pressure overload and to study whether endothelin-1 or angiotensin II plays a causal role in the activation of cardiac AM gene expression. The pressure overload was produced by arginine-vasopressin (AVP, 0.05 μg/kg per minute IV) infusion for 15 minutes, 30 minutes, 1 hour, 2 hours, or 4 hours in conscious rats. A significant increase in left ventricular AM mRNA levels was seen after 2 hours of pressure overload in the left ventricle and after 30 minutes in the left atrium. The left atrial immunoreactive AM (ir-AM) levels decreased significantly after 2 hours of pressure overload. Plasma ir-AM levels increased slightly in response to 4 hours of AVP infusion. Bolus injections of bosentan (mixed ETA/ETB receptor antagonist, 10 mg/kg IV), losartan (AT1 receptor antagonist, 10 mg/kg IV), and their combination had no effect on the increase of cardiac AM mRNA and ir-AM levels produced by 2 hours of pressure overload. In addition, losartan, bosentan, and their combination did not affect plasma ir-AM levels in the vehicle-infused and AVP-infused animals. The present study indicates that cardiac AM gene expression is rapidly upregulated in response to pressure. The induction of ventricular and atrial AM gene expression by pressure overload is angiotensin II-independent and endothelin-1-independent.

Original languageEnglish
Pages (from-to)84-90
Number of pages7
JournalHypertension
Volume37
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

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Keywords

  • Adrenomedullin
  • Angiotensin II
  • Endothelin
  • Gene expression

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Romppanen, H., Puhakka, J., Földes, G., Szokodi, I., Vuolteenaho, O., Tokola, H., Tóth, M., & Ruskoaho, H. (2001). Endothelin-1-independent and angiotensin II-independent induction of adrenomedullin gene expression. Hypertension, 37(1), 84-90. https://doi.org/10.1161/01.HYP.37.1.84