| Acute cardiovascular effects of the calcimimetic R-568 and its enantiomer S-568 in rats. | |
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MedLine Citation:
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PMID: 19280225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcimimetics increase the sensitivity of the calcium sensing receptor (CaSR) to calcium ions (Ca(2+)) and allow for efficient control of uraemic hyperparathyroidism. Recent studies suggested an additional blood pressure-lowering action, the underlying mechanisms are as yet unknown. We infused R-568 and its enantiomer S-568, which has little activity at the CaSR, in anaesthetized rats. Mean arterial blood pressure (MAP) and heart rate (HR) were measured in the femoral artery; renal blood flow (RBF) and mesenteric blood flow (MBF) were measured locally. Infusion of R-568 at 0.7 mg/kg per 10 min into the femoral vein, a dose known to reduce levels of parathyroid hormone (PTH) and Ca(2+) in plasma, did not affect blood pressure or heart rate. Infusion of 2.1 mg/kg per 3 min of R-568 and S-568 into the femoral vein significantly reduced MAP by 26 +/- 4.5 and 23.7 +/- 3.1% and HR by 7.8 +/- 2.9 and 5.8 +/- 2.0%, respectively. Intra-arterial infusions of R-568 increased blood flow in a dose-dependent fashion. At plasma concentrations of 70 micromol/l R-568 and S-568 increased RBF by 17 +/- 3 and 15 +/- 3% and MBF by 28 +/- 5 and 29 +/- 5%. The effects on blood flow were greater in the mesenteric artery than in the renal artery, but not different between both compounds.The calcimimetic R-568 exerts acute, CaSR-independent, hypotensive effects via vasodilation and negative chronotropy at concentrations exceeding those required for modulation of PTH secretion. |
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Authors:
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Kumiko Nakagawa; Niru Parekh; Nadezda Koleganova; Eberhard Ritz; Franz Schaefer; Claus Peter Schmitt |
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Publication Detail:
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Type: Journal Article Date: 2009-03-12 |
Journal Detail:
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Title: Pediatric nephrology (Berlin, Germany) Volume: 24 ISSN: 1432-198X ISO Abbreviation: Pediatr. Nephrol. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-01 Completed Date: 2009-08-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8708728 Medline TA: Pediatr Nephrol Country: Germany |
Other Details:
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Languages: eng Pagination: 1385-9 Citation Subset: IM |
Affiliation:
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Division of Paediatric Nephrology, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aniline Compounds
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administration & dosage*,
chemistry Animals Blood Pressure / drug effects Cardiovascular System / drug effects Dose-Response Relationship, Drug Heart Rate / drug effects Male Rats Rats, Sprague-Dawley Receptors, Calcium-Sensing / drug effects Renal Circulation / drug effects Splanchnic Circulation / drug effects* Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Aniline Compounds; 0/N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; 0/Receptors, Calcium-Sensing |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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