Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.
Animal ; Aorta/drug effects/physiology ; In Vitro ; Membrane Potentials/drug effects ; Potassium/pharmacology ; Potassium Channels/physiology ; Rabbits ; Support, Non-U.S. Gov't ; Tetraethylammonium Compounds/pharmacology ; Vanadates/*pharmacology ; Vasodilation/*drug effects

Peripheral nerve injury sometimes leads to neuropathic pain and depletion of calcitonin gene related-peptide (CGRP) and substance P (SP) in the spinal cord. However, the pathophysiological mechanisms for depletion of CGRP and SP following the neuropathic injury are still unknown. This study was performed to see whether the distribution of immunoreactivity for CGRP and SP in the superficial dorsal horn and dorsal root ganglia (DRG) was related to the distance between the DRG and injury site. To this aim, we compared two groups of rats; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerve (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunostaining with SP and CGRP antibody was done in the S1-S3 spinal cord and DRG of the two groups 1 and 12 weeks after the injury. The results obtained are as follows: 1. The immunoreactivity for CGRP and SP in the ipsilateral superficial dorsal horn and DRG decreased 1 and 12 weeks after neuropathic nerve injury. 2. The immunoreactive area of SP and CGRP in the S1 dorsal horn was smaller in the S123 group than in the S34 group, whereas that in the S3 dorsal horn was not significantly different between the two groups. The number of SP- immunoreactive DRG cells decreased on the neuropathic side as compared to the sham group's in all DRGs of experimental groups except the S1 DRG of the S34 group. These results suggest that the amounts of SP and CGRP in the dorsal horn and DRG following neuropathic injury inversely decrease according to the distance between the DRG and injury site.
Animals ; Calcitonin ; Diagnosis-Related Groups* ; Ganglia, Spinal ; Horns ; Hyperalgesia ; Neuralgia ; Peripheral Nerve Injuries ; Rats* ; Spinal Cord* ; Spinal Nerves ; Substance P ; Tail