Vasodilator effect of Cassiarin A, a novel antiplasmodial alkaloid from Cassia siamea, in rat isolated mesenteric artery.
The aim of this study was to investigate the vasorelaxant effect induced by cassiarin A, a novel antiplasmodial alkaloid from Cassia siamea, in rings cut from rat superior mesenteric arteries. In rings precontracted with phenylephrine, cassiarin A induced a concentration-dependent relaxation. This relaxation was attenuated: 1) after removal of the endothelium or after pretreatment of rings with 100 microM of N(G)-nitro-L-arginine (nitric oxide synthase inhibitor) or 10 microM of 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (guanylyl cyclase inhibitor), but not after pretreatment with 10 microM of indomethacin (cyclooxygenase inhibitor); and 2) after pretreatment of preparations with either a nonselective or selective inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels [1 mM of tetraethylammonium or 100 nM of iberiotoxin, respectively]. The cassiarin A-induced relaxation was also attenuated by these BK(Ca) inhibitors in endothelium-denuded preparations. The cassiarin A-induced relaxation was not altered by treatment with the ATP-sensitive K(+)-channel inhibitor glibenclamide (10 microM) or with the voltage-dependent K(+)-channel inhibitor 4-aminopyridine (1 mM). In isolated mesenteric artery rings, cassiarin A tended to increase nitric oxide (NO) levels. These results suggest that in the rat mesenteric artery, cassiarin A-induced relaxation may be mediated by endothelial NO and may occur partly via BK(Ca)-channel activation.
Matsumoto
Takayuki
T
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Kobayashi
Tsuneo
T
Ishida
Keiko
K
Hirasawa
Yusuke
Y
Morita
Hiroshi
H
Honda
Toshio
T
Kamata
Katsuo
K
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002366:Cassia / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents / Q000494:pharmacology*
D000470:Alkaloids; D000962:Antimalarials; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C524027:cassiarin A; D010656:Phenylephrine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester