Novel method for localized, functional sympathetic nervous system denervation of peripheral tissue using guanethidine

A simple technique for local chemical sympathectomy of peripheral tissues i s described using guanethidine. Multiple microinjections of guanethidine we re made into inguinal or epididymal white adipose tissue (IWAT and EWAT) pa ds or spleens of hamsters. Guanethidine virtually abolished the sympathetic innervation of both EWAT and IWAT, as measured by the absence of significa nt norepinephrine (NE) tissue content two weeks later and as suggested by t he two-fold increase in IWAT mass characteristic of surgically induced WAT denervation. These measures were not affected in the contralateral pads giv en equivolumetric injections of saline. Guanethidine injections into the sp leen lead to a functional sympathectomy, as indicated by significant deplet ions of NE content. Because guanethidine treatment did not decrease body ma ss, induce ptosis, or spread to closely associated adjacent tissue (contral ateral EWAT pad), no chemical-induced malaise or global sympathetic denerva tion was suggested. Guanethidine was more effective than two other local sy mpathectomy treatments, injections of the sympathetic neurotoxin anti-dopam ine-beta -hydroxylase saporin or surgical denervation, in decreasing IWAT N E content and increasing IWAT pad mass. Collectively, these results suggest that locally applied, chemical sympathectomy with guanethidine provides an effective, restricted method for sympathectomizing WAT, spleen and likely other peripheral tissues. (C) 2001 Elsevier Science B.V. All rights reserve d.