Induction of functional bradykinin B1-receptors in normotensive rats and mice under chronic angiotensin-converting enzyme inhibitor treatment

Maria E. Marin-Castaño, Joost P. Schanstra, Eric Neau, Françoise Praddaude, Christiane Pecher, Jean Louis Ader, Jean Pierre Girolami, Jean Loup Bascands

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Background - The physiological effects of ACE inhibitors may act in part through a kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor treatment on functional kinin B1- and B2-receptor expression, which are the molecular entities responsible for the biological effects of kinins. Methods and Results - Rats were subjected to different 6-week treatments using various mixtures of the following agents: ACE inhibitor, angiotensin AT1-receptor antagonist, and B1 and B2-receptor antagonists. Chronic ACE inhibition induced both renal and vascular B1-receptor expression, whereas B2-receptor expression was not modified. Furthermore, with B1-receptor antagonists, it was shown that B1-receptor induction was involved in the hypotensive effect of ACE inhibition. Using microdissection, we prepared 10 different nephron segments and found ACE-inhibitor-induced expression of functional B1-receptors in all segments. ACE-inhibitor-induced B1-receptor induction involved homologous upregulation, because it was prevented by B1-receptor antagonist treatment. Finally, using B2-receptor knockout mice, we showed that ACE-inhibitor-induced B1-receptor expression was B2-receptor independent. Conclusions - This study provides the first evidence that chronic ACE-inhibitor administration is associated with functional vascular and renal B1-receptor induction, which is involved in ACE- inhibitor-induced hypotension. The observed B1-receptor induction in the kidney might participate in the known renoprotective effects of ACE inhibition.

Original languageEnglish (US)
Pages (from-to)627-632
Number of pages6
JournalCirculation
Volume105
Issue number5
DOIs
StatePublished - Feb 5 2002

Keywords

  • Angiotensin-converting enzyme
  • Blood pressure
  • Bradykinin
  • Kidney

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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