Mechanisms of vasorelaxation induced by Ziziphora clinopodioides Lam. (Lamiaceae) extract in rat thoracic aorta.
OBJECTIVE
Ziziphora clinopodioides Lam. (ZC) is widely used in Uyghur folk medicine for the treatment of hypertension diseases in Xinjiang, an autonomous region of China. To provide pharmacological basis for this traditional use, we explored the vasodilating effects of ZC and investigated the underlying mechanisms.


METHODS
Activity of hexane (ZCHE), dichloromethane (ZCDE) and aqueous (ZCAE) extracts of ZC were evaluated on isolated rat aortic rings pre-contracted with phenylephrine (PE) or high KCl. The mechanisms were evaluated on ZCDE, the most potent extract.


RESULTS
ZCDE-induced relaxation in endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 10(-6) M) or high KCl (6×10(-2) M), with respective EC(50) values of 0.27±0.03 and 0.34±0.04 g/l. Mechanic removal of the endothelium did not significantly modify ZCDE-induced relaxation. In endothelium-denuded aorta pre-contracted with PE (10(-6) M), the vasorelaxant effect of ZCDE was significantly decreased by 4-amino-pyridine (10(-3) M), but not by glibenclamide (10(-4) M), iberiotoxin (3×10(-8) M) and thapsigargin (10(-7) M). In Ca(2+) free solution, ZCDE significantly inhibited extracellular Ca(2+)-induced contraction in high KCl and PE pre-contracted rings. Additionally ZDCE inhibited the intracellular Ca(2+) release sensitive to PE (10(-6) M).


CONCLUSIONS
The results demonstrate that ZDCE exhibits endothelium-independent vasodilating properties that are mediated by inhibition of extracellular Ca(2+) influx through voltage- and receptor-operated Ca(2+) channels (VDDCs and ROCCs), by inhibition of Ca(2+) release from intracellular stores, and also by the opening of voltage-dependent K(+) channels.
Senejoux
François
F
EA 4267 Sciences Séparatives, Biologiques et Pharmaceutiques, UFR des Sciences Médicales et Pharmaceutiques, 25030 Besançon, France.
Girard
Corinne
C
Kerram
Parhat
P
Aisa
Haji Akber
HA
Berthelot
Alain
A
Bévalot
Françoise
F
Demougeot
Céline
C
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D002118:Calcium