Calcium-sensing receptors modulate renin release in vivo and in vitro in the rat.

Détails

ID Serval
serval:BIB_8725B8D77CC8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Calcium-sensing receptors modulate renin release in vivo and in vitro in the rat.
Périodique
Journal of Hypertension
Auteur(s)
Maillard M.P., Tedjani A., Perregaux C., Burnier M.
ISSN
1473-5598[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
27
Numéro
10
Pages
1980-1987
Langue
anglais
Résumé
OBJECTIVES: Calcium-sensing receptors (CaSRs) have been localized in the juxtaglomerular apparatus where they may contribute to the regulation of renin release. In the present study, we investigated the in-vitro and in-vivo effects of the calcimimetic R-568 on renin release. METHODS: In vitro, the effect of calcimimetics on renin release was assessed by incubating freshly isolated rat juxtaglomerular cells with or without R-568 (1 and 10 mumol/l) in serum-free medium in the presence or absence of forskolin or CaCl2. In vivo, we measured the impact of R-568 (20 ng/min intravenously) on the acute changes in plasma renin activity (PRA) induced by either a 90 min infusion of the angiotensin-converting enzyme inhibitor captopril, or the beta-receptor agonist isoproterenol, or of a vehicle in or after a furosemide challenge in conscious Wistar rats. RESULTS: In vitro, R-568 dose-dependently blunted renin release, but also reduced the increase in renin due to forskolin (P < 0.01). Both isoproterenol and enalapril increased in vivo PRA to 3.1 +/- 0.3 and 3.7 +/- 0.5 ng Ang I/ml per h, respectively (P < 0.01), compared with vehicle (1.5 +/- 0.2 ng Ang I/ml per h). R-568 significantly reduced PRA to 2.1 +/- 0.1 ng/ml per h in isoproterenol-treated rats and to 1.6 +/- 0.2 ng/ml per h in enalapril-treated rats (P < 0.05). In low-salt treated animals, acute infusion of furosemide increased PRA from 8.7 +/- 3.2 to 18.6 +/- 2.3, whereas R-568 partially blunted this rise to 11.2 +/- 1.5 (P = 0.02). In vivo, R-568 significantly lowered serum calcium and PTH1-84, but the drug-induced changes in PRA were independent of the changes in calcium and parathyroid hormone. CONCLUSION: After the recent discovery of CaSRs in juxtaglomerular cells of mice, our results confirm the presence of such receptors in rats and demonstrate that these receptors modulate renin release both in vitro and in vivo. This suggests that CaSRs play a role as a regulatory pathway of renin release.
Mots-clé
Calcimimetics, Calcium-Sensing Receptor , Enalapril, In-Vivo Modulation, Isoproterenol, Juxtaglomerular Cell, R-568, Rat, Renin
Pubmed
Web of science
Création de la notice
28/10/2009 10:15
Dernière modification de la notice
20/08/2019 14:46
Données d'usage