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 language | English |
|---|---|
| Pages (from-to) | 627-632 |
| Number of pages | 6 |
| Journal | Circulation |
| Volume | 105 |
| Issue number | 5 |
| DOIs | |
| State | Published - Feb 5 2002 |
| Externally published | Yes |
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Keywords
- Angiotensin-converting enzyme
- Blood pressure
- Bradykinin
- Kidney
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Induction of functional bradykinin B1-receptors in normotensive rats and mice under chronic angiotensin-converting enzyme inhibitor treatment. / Marin-Castaño, Maria E.; Schanstra, Joost P.; Neau, Eric; Praddaude, Françoise; Pecher, Christiane; Ader, Jean Louis; Girolami, Jean Pierre; Bascands, Jean Loup.
In: Circulation, Vol. 105, No. 5, 05.02.2002, p. 627-632.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of functional bradykinin B1-receptors in normotensive rats and mice under chronic angiotensin-converting enzyme inhibitor treatment
AU - Marin-Castaño, Maria E.
AU - Schanstra, Joost P.
AU - Neau, Eric
AU - Praddaude, Françoise
AU - Pecher, Christiane
AU - Ader, Jean Louis
AU - Girolami, Jean Pierre
AU - Bascands, Jean Loup
PY - 2002/2/5
Y1 - 2002/2/5
N2 - 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.
AB - 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.
KW - Angiotensin-converting enzyme
KW - Blood pressure
KW - Bradykinin
KW - Kidney
UR - http://www.scopus.com/inward/record.url?scp=0037022211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037022211&partnerID=8YFLogxK
U2 - 10.1161/hc0502.102965
DO - 10.1161/hc0502.102965
M3 - Article
C2 - 11827930
AN - SCOPUS:0037022211
VL - 105
SP - 627
EP - 632
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 5
ER -