RELAXIN DEPRESSES PLATELET-AGGREGATION - IN-VITRO STUDIES ON ISOLATEDHUMAN AND RABBIT PLATELETS

BACKGROUND: Relaxin, a peptide hormone of ovarian origin, has been sho wn to cause a striking dilatory action on microvessels in different or gans. In our recent studies, relaxin has been shown to stimulate the p roduction of nitric oxide, a powerful vasodilatory agent, in several t argets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function. EXPERIMENTAL DESIGN: The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with r elaxin at different concentrations and then stimulated with collagen o r thrombin. Aggregation and intracellular levels of cGMP and Ca2+ were determined. In some experiments, inhibitors or potentiators of nitric oxide activity were also used to clarify whether the mechanism of act ion of relaxin involves the L-arginine-nitric-oxide pathway. Electron microscopy of platelets treated and not treated with relaxin was also carried out. RESULTS: Preincubation of the platelets with relaxin befo re stimulation with proaggregants resulted in a significant, concentra tion-dependent inhibition of platelet aggregation, accompanied by an e levation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through ni tric oxide. Ultrastructurally, relaxin was shown to hinder the conform ational changes and granule exocytosis usually occurring in platelets during aggregation. CONCLUSIONS: This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive a ctivities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic a nd hypertensive disorders of pregnancy and cardiovascular diseases.