Journal of Clinical and Experimental Ophthalmology
Open Access

Abstract

Timolol Modulates Erythrocyte Nitric Oxide Bioavailability

Carlota Saldanha, Pedro Teixeira, Santos-Freitas T and Patrícia Napoleão

Changes of oxygen partial pressure in tissues are sensed by the erythrocytes that with the efflux or with the maintenance of nitric oxide that contains promote vasodilation or vasoconstriction. Binding of acetylcholine with the acetylcholinesterase of the erythrocyte membrane originates a signal transduction mechanism that involves both the Gi protein as well as band 3 protein what stimulates nitric oxide efflux. The bioavailability of nitric oxide in presence of velnacrine maleate an inhibitor of acetylcholinesterase is preserved what means that there are no changes in the nitric oxide efflux. Timolol maleate is an inhibitor of acetylcholinesterase.
The aim of this study was to assess the role of the timolol maleate in the erythrocyte in respect to bioavailability on nitric oxide and compare it with effect resulting of the presence of acetylcholine. Venous blood samples were collected from the forearm vein of fifteen healthy Caucasian men after informed consent. Each blood sample was divided in three 1 mL samples, centrifuged, and suspensions of erythrocyte were performed in order to achieve 10 μM final concentration either of acetylcholine or of the timolol. Levels of nitric oxide efflux were evaluated by amperometric method. S-nitrosoglutathione, nitrites and nitrates were assessed with the Griess reaction using the spectrophotometric method.
The nitric oxide efflux by the erythrocyte in presence of timolol is like to the control sample but significantly decreased it when compared to the sample with acetylcholine. The presence of timolol induces decrease in the erythrocyte levels of S-nitrosoglutathione significantly in relation with the control and with acetylcholine samples.
In conclusion, in vitro, in erythrocyte the nitric oxide content is maintained by timolol maleate. It may be expected the same role for timolol in the ocular microcirculation when being applied as a therapeutic compound.