(081) Comparing the Contributions of Nitric Oxide and Estrogen to Methamphetamine-Induced Alterations of Vaginal Blood Flow in Rats

Abstract

Abstract Introduction Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms utilizing this physiology. Previous research from our lab has demonstrated that female methamphetamine (meth) users experience the production of excessive vaginal lubrication immediately following an intravenous injection of methamphetamine, and we have recapitulated this in an anesthetized rodent model. We have also found that this vaginal lubrication, as well as vaginal blood flow increased by meth, are heavily nitric oxide dependent. Objective The purpose of the current study is to determine if increased vaginal blood flow correlates with increased vaginal lubrication in response to meth, and to determine if alterations in this blood flow are dependent upon nitric oxide, estrogen, or both. Methods Adult female Wistar rats were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with meth or saline via the implanted catheter. Vaginal blood flow, measured using a Periflux System 5000 and a small laser probe inserted 5-10 mm into the vaginal canal, was continuously recorded before and for at least twenty minutes following drug administration. After establishing meth-induced alterations in vaginal blood flow, rats were pre-treated with L-NG-Nitro arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or fulvestrant, an estrogen receptor antagonist, followed by meth administration using the same procedure for measuring blood flow to determine the contribution of nitric oxide and estrogen. Results Meth immediately increases vaginal blood flow, followed by a decrease in perfusion, which is characteristic of a drug that induces such profound sympathetic activation. L-NAME reduced meth-induced increases in vaginal blood flow, and we predict that fulvestrant will be less effective. Conclusions Nitric oxide and estrogen are molecules critical to the production of vaginal lubrication. Nitric oxide, important for the vasodilation cascade leading to the production of vaginal transudate, contributes to meth-induced increases in vaginal blood flow and vaginal lubrication. Estrogen signaling likely contributes to meth-induced increases in vaginal blood flow, and thus, vaginal lubrication, but not as substantially as nitric oxide, making nitric oxide a better potential target for those suffering from vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Embera NeuroTherapeutics & JanOne, both affiliations unrelated to current research