17 Beta-estradiol-stimulated nitric oxide production by neutrophils: effect on platelet activation

Abstract

Objective: To evaluate the effect of 17beta-estradiol (E2) on the ability of human neutrophils to produce nitric oxide (NO) and its effects on platelet activation.

Methods: The expression of neuronal nitric oxide synthase (nNOS) protein and the formation of NO by 17beta-E2-incubated neutrophils from men were studied in vitro (ten male volunteers, no medical-surgical antecedents, aged 25-45 years). Platelet aggregometry and changes in cyclic guanosine monophospate (cGMP) levels were used to bioassay the functionality of NO released from neutrophils.

Results: Incubation of neutrophils derived from men with physiologic concentrations of 17beta-E2 (10(-10) to 10(-8) mol/L) enhanced the expression of nNOS protein. 17Beta-E2-incubated neutrophils also showed a significant increase in their ability to generate NO measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. Furthermore, 17beta-E2-incubated neutrophils showed a greater ability to prevent adenosine diphosphate (ADP)-induced platelet activation. Moreover, increased levels of cGMP were found in the coincubation of platelets with 17beta-E2-treated neutrophils.

Conclusion: These results suggest that 17beta-E2 increases the ability of human neutrophils to produce NO and therefore may contribute to cardiovascular disease protection.