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The L-Arginine-Nitric Oxide System Regulates Platelet Aggregation in Pregnancy

Departments of Obstetrics and Gynecology and Hematology, University of Modena, Modena, Italy facchi{at}unimo.it

Marco Marietta, MD

Federica Piccinini, MD

Annibale Volpe, MD

Fabio Facchinetti, MD

Departments of Obstetrics and Gynecology and Hematology, University of Modena, Modena, Italy

Objective: To investigate the ex vivo platelet aggregation in response to a substrate (L-arginine [L-Arg]) and a donor (sodium nitroprusside [SN]) of nitric oxide (NO) in nonpregnant women and in normotensive pregnancies.

Methods: Platelet aggregation was studied with a dual-channel aggregometer and expressed as a percentage of light transmission. Measurements were done at baseline and after preincubation with scalar doses of L-Arg and SN. The intraplatelet L-citrulline (L-Cit) levels were measured by high-performance liquid chromatography (HPLC).

Results: In both groups, the baseline aggregation values were similar for adenosine diphosphate (ADP) and collagen stimuli. Wilcoxon rank-sum testing demonstrated that in both groups the addition of L-Arg had a significant effect on aggregation: Doses of 50 to 5000 µmol decreased ADP-induced aggregation. Conversely, collagen-induced aggregation was affected only by the highest dose of L-Arg. Sodium nitroprusside administered in doses of 2.5 to 250.0 nmol decreased ADP- and collagen-induced platelet aggregation equally. ADP-induced aggregation values obtained after (SN) incubation were positively correlated with gestational age. Intraplatelet L-Cit levels showed a significant rise after the incubation with L-Arg, and this effect was negatively correlated with gestational age.

Conclusion: The L-Arg-NO system regulates platelet aggregation during pregnancy. Moreover, a physiologic reduction of platelet sensitivity to the antithrombotic effect of NO occurs.

Journal of the Society for Gynecologic Investigation, Vol. 5, No. 4, 192-196 (1998)
DOI: 10.1177/107155769800500406


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