Fibrinogen effects of erythrocyte nitric oxide metabolism in presence of timolol

Abstract

Timolol inhibits erythrocyte membrane acetylcholinesterase (AChE) enzyme activity originates less active enzyme complex forms unable to change the normal values of the nitric oxide (NO) efflux from erythrocytes. The active complex resulting from acetylcholine (ACh) binding to AChE induces higher values of NO efflux. Increased values of NO efflux were also observed in presence of high fibrinogen (Fib) concentration with return to normal levels of NO efflux when ACh is added. Association between NO efflux and erythrocyte deformability values has been evidenced. The objective of this study was to evaluate the effects of high fibrinogen concentration on the erythrocyte NO metabolism and deformability in presence of timolol without and plus adenylyl cyclase or plus guanylyl cyclase inhibitors. Blood samples from healthy donors were divided in aliquots without (control) or with Fib or Fib plus timolol in absence or presence of adenylyl cyclase inhibitor (MDL) or guanylyl cyclase inhibitor (Ly). Erythrocyte deformability (ED), NO efflux, S-nitrosoglutathione (GSNO), nitrite and nitrate values were evaluated by referenced methods. Fib increased the values of NO efflux under the influence of timolol or MDL. Increased values of NO efflux, GSNO, nitrites and nitrates where obtained in presence of Fib plus timolol plus MDL in relation to control to Fib or Fib plus MDL aliquots. Increased nitrites and nitrates values where obtained in presence of Fib plus timolol plus Ly in relation to control, to Fib and Fib plus Ly. Only at high shear stress increased ED values was observed in Fib plus timolol in absence and presence of MDL. In conclusion fibrinogen plus timolol increased ED at high shear stress without or with MDL. Fibrinogen increased NO efflux from erythrocytes and GSNO, nitrite and nitrate levels in presence of timolol plus guanylyl cyclase inhibitor.