Abstract |
The protective effect of YM-254890, a specific Galphaq/11 inhibitor, on laurate-induced peripheral arterial disease in rats was compared with those of prostaglandin E1 ( PGE1), beraprost, and clopidogrel. YM-254890 inhibited ADP-induced ex vivo rat platelet aggregation at a dose of 3 microg/kg. Furthermore, YM-254890 strongly inhibited phenylephrine-, serotonin- and endothelin-1-induced contractions in the rat aorta, and improved dermal blood flow after the laurate injection. The intra-arterial single bolus administration of YM-254890 15 min after the laurate injection dose-dependently inhibited the progression of the lesion, with significance, at 3 microg/kg without affecting systemic blood pressure. PGE1 and beraprost, when administered before the laurate injection, were effective, but their potencies were less than that of YM-254890. Clopidogrel significantly suppressed lesion progression when administered at 30 mg/kg twice a day for 3 days, which completely inhibited platelet aggregation. These results suggest that the local administration of YM-254890 may be useful for treating peripheral arterial disease.
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Authors | Toshio Uemura, Hajime Takamatsu, Tomihisa Kawasaki, Masatoshi Taniguchi, Eisaku Yamamoto, Yuichi Tomura, Wataru Uchida, Keiji Miyata |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 536
Issue 1-2
Pg. 154-61
(Apr 24 2006)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 16566917
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Lauric Acids
- Peptides, Cyclic
- Platelet Aggregation Inhibitors
- Vasodilator Agents
- YM-254890
- lauric acid
- beraprost
- Clopidogrel
- Epoprostenol
- GTP-Binding Protein alpha Subunits, Gq-G11
- Ticlopidine
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Topics |
- Animals
- Aorta
(drug effects, physiology)
- Blood Flow Velocity
(drug effects)
- Blood Pressure
(drug effects)
- Clopidogrel
- Dermis
(blood supply, drug effects)
- Dose-Response Relationship, Drug
- Endothelium, Vascular
(physiology)
- Epoprostenol
(analogs & derivatives, pharmacology)
- GTP-Binding Protein alpha Subunits, Gq-G11
(antagonists & inhibitors)
- Heart Rate
(drug effects)
- Hindlimb
(blood supply, drug effects)
- In Vitro Techniques
- Lauric Acids
- Male
- Peptides, Cyclic
(pharmacology)
- Peripheral Vascular Diseases
(chemically induced, pathology, prevention & control)
- Platelet Aggregation
(drug effects)
- Platelet Aggregation Inhibitors
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Ticlopidine
(analogs & derivatives, pharmacology)
- Vasodilation
(drug effects)
- Vasodilator Agents
(pharmacology)
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