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The hypotensive agent dodoneine inhibits L-type Ca2+ current with negative inotropic effect on rat heart
- Source :
- European Journal of Pharmacology, European Journal of Pharmacology, Elsevier, 2014, 728, pp.119-27. ⟨10.1016/j.ejphar.2014.01.059⟩
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- International audience; Agelanthus dodoneifolius is one of the medicinal plants used in African pharmacopeia and traditional medicine for the treatment of cardiovascular diseases. A chemical analysis has identified one of the active principles: Dodoneine (Ddn). It is a new dihydropyranone which exerts hypotensive and vasorelaxant effects on rat. Since the mechanism of the hypotensive effect is unknown, we performed a variety of preclinical and mechanistic studies to characterize the specific cardiac effect of Ddn at tissue (ex-vivo) and cellular levels (in-vitro) in order to determine a molecular target. Ddn effects were evaluated in an isolated rat heart preparation using Langendorff retrograde perfusion and then, the effects of Ddn were characterized in freshly dissociated cardiac ventricular myocytes using the whole-cell patch-clamp configuration. Ex-vivo, Ddn produced a dose-dependent negative inotropic effect with an IC50 value of 10 µM without changed heart rate. 100 µM Ddn decreased left ventricular developed pressure of about 40%. In isolated cardiac myocytes, Ddn reduced I(Ca),L density of about 30% with an IC50 value estimated at 3 µM. Ddn did not change current-voltage relation but it shifted the inactivation curve toward negative potentials and modified the half inactivation potentials. Furthermore, Ddn induced a phasic-dependent blocking on ICa,L. This study demonstrates that the hypotensive property of dodoneine is likely associated with a negative inotropic effect and the blockade of the L-type calcium channels.
- Subjects :
- Male
Inotrope
medicine.medical_specialty
Patch-Clamp Techniques
Calcium Channels, L-Type
Heart Ventricles
[SDV]Life Sciences [q-bio]
In Vitro Techniques
Pharmacology
Loranthaceae
Membrane Potentials
Phenols
Internal medicine
Heart rate
Ventricular Pressure
medicine
Retrograde perfusion
Animals
Myocyte
Myocytes, Cardiac
Rats, Wistar
Medicine, African Traditional
IC50
Antihypertensive Agents
Voltage-dependent calcium channel
business.industry
Rat heart
Myocardial Contraction
Rats
3. Good health
Blockade
Endocrinology
Pyrones
business
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 728
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....4144f55d8c894e62a9efce985f4f43df