Specific augmentation of plantar skin blood flow by lipo-PGE1 assessed in tetrodotoxin- and NG-nitro-L-arginine treated rats

Vasodilating effects of prostaglandin E-1 incorporated in lipid microspheres (lipo-PGE(1)) were compared with those of prostaglandin E-1 (PGE(1)) or its cyclodextrin clathrated preparation (PGE(1)-CD) on plantar skin blood flow in rats treated with tetrodotoxin and N-G-nitro-L-arginine (L-NNA). Tetrodotoxin (50 mu g/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, r-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-PGE(1) increased planter skin blood flow 4 to 6 times more potently than PGE(1)-CD or PGE(1) in the treated rats. Furthermore, lipo- PGE(1) increased plantar skin blood flow about 3 times more selectively than PGE(1)-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 PGE(1) preparations, especially lipo-PGE(1) could potently and selectively increase plantar skin blood flow in rats treated with tetrodotoxin and L-NNA.