Specific augmentation of plantar skin blood flow by lipo-PGE1 assessed in tetrodotoxin- and N(G)-nitro-L-arginine-treated rats.
1Vasodilating effects of prostaglandin E1 incorporated in lipid microspheres (lipo-PGE1) were compared with those of prostaglandin E1 (PGE1) or its cyclodextrin clathrated preparation (PGE1-CD) on plantar skin blood flow in rats treated with tetrodotoxin and N(G)-nitro-L-arginine (L-NNA). Tetrodotoxin (50 microg/kg, i.v.) could totally inhibit the pressor response to electrical stimulation of the spinal cord, and the reflex tachycardia due to the depressor response to acetylcholine. Furthermore, L-NNA (30 mg/kg, i.v.) was used to counteract the lowering of the systemic blood pressure and peripheral vascular tone by elimination of sympathetic nerve activity, and to maintain the arterial blood pressure at the control level. Lipo-PGE1 increased plantar skin blood flow 4 to 6 times more potently than PGE1-CD or PGE1 in the treated rats. Furthermore, lipo-PGE1 increased plantar skin blood flow about 3 times more selectively than PGE1-CD. We also assessed several vasodilators, including terbutaline, nitroprusside, nicardipine, and papaverine in tetrodotoxin- and L-NNA-treated rats. However, none of them could selectively increase plantar blood flow despite the prominent depressor responses achieved. These results suggest that PGE1 preparations, especially lipo-PGE1 could potently and selectively increase plantar skin blood flow in rats treated with tetrodotoxin and L-NNA.
Chino
D
D
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Japan.
Akimaru
S
S
Kataha
K
K
Ishii
K
K
Nakayama
K
K
D000109:Acetylcholine; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot / Q000098:blood supply / Q000294:innervation; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects*; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D047391:alpha-Cyclodextrins; C043214:prostaglandin E1-alpha-cyclodextrin; D019335:Nitroarginine; D013779:Tetrodotoxin; D000527:Alprostadil; D000109:Acetylcholine