Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets.
BACKGROUND
Relaxin, a peptide hormone of ovarian origin, has been shown to cause a striking dilatory action on microvessels in different organs. In our recent studies, relaxin has been shown to stimulate the production of nitric oxide, a powerful vasodilatory agent, in several targets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function.


METHODS
The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with relaxin at different concentrations and then stimulated with collagen or 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 action 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 before stimulation with proaggregants resulted in a significant, concentration-dependent inhibition of platelet aggregation, accompanied by an elevation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through nitric oxide. Ultrastructurally, relaxin was shown to hinder the conformational changes and granule exocytosis usually occurring in platelets during aggregation.


CONCLUSIONS
This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive activities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic and hypertensive disorders of pregnancy and cardiovascular diseases.
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006152:Cyclic GMP / Q000097:blood; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D012065:Relaxin / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D012065:Relaxin; D003094:Collagen; D019001:Nitric Oxide Synthase; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium