Pharmacologic analysis of 7-O-ethyl-fangchinoline-induced vasodilation properties in isolated perfused common carotid arteries of Wistar Kyoto rats and spontaneously hypertensive rats.
Using the cannula insertion method, we investigated vascular effects of 7-O-ethyl-fangchinoline (TJN-220) derived from tetrandrine in isolated and perfused common carotid arteries of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). A single dose of TJN-220 caused a vasodilation in a dose-related manner in arteries preconstricted by phenylephrine. The vasodilation was not inhibited by propranolol, a potent beta-adrenoceptor antagonist. A potent alpha-antagonist bunazosin inhibited the vasoconstriction to norepinephrine while TJN-220 did not modify the norepinephrine-induced constriction, indicating TJN-220 had no alpha-blocking activity. A potent calcium entry blocker, diltiazem, markedly attenuated the KCl-induced vasoconstriction, and TJN-220 slightly but significantly attenuated the KCl-induced one in large doses. The vasodilation of TJN-220 was not abolished after removing the endothelium by an intraluminal administration of saponin, although the ACh-induced dilation was completely abolished by it. A comparison of vascular responses in WKY and SHR revealed no significant differences. From these results, it is concluded that 1) a new tetrandrine derivative, TJN-220 has relatively long-lasting vasorelaxant properties, 2) the dilatory effects might not be related to adrenergic, muscarinic or endothelium-dependent mechanisms, and 3) the effects might partially be due to calcium entry antagonistic properties.
Matsuura
M
M
Department of Hospital Pharmacy, Shinshu University School of Medicine, Nagano, Japan.
Zenda
H
H
Chiba
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D044182:Benzylisoquinolines; D002339:Carotid Arteries / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000470:Alkaloids; D044182:Benzylisoquinolines; D011799:Quinazolines; D014665:Vasodilator Agents; C069407:7-O-ethyl fangchinoline; D010656:Phenylephrine; D001285:Atropine; C018176:bunazosin; D011433:Propranolol; D004110:Diltiazem; D007545:Isoproterenol