Bani D, Bigazzi M, Masini E, Bani G, Sacchi T B
Department of Human Anatomy, University of Florence, Italy.
Lab Invest. 1995 Nov;73(5):709-16.
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.
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.
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.
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.
松弛素是一种源自卵巢的肽类激素，已被证明可对不同器官的微血管产生显著的舒张作用。在我们最近的研究中，松弛素已被证明可在多个靶标中刺激一氧化氮（一种强大的血管舒张剂）的产生。一氧化氮还可抑制血小板聚集。这促使我们探究松弛素在血小板功能中的作用。
在分离的人及兔血小板中研究了松弛素对血小板聚集的影响。将样品与不同浓度的松弛素孵育，然后用胶原蛋白或凝血酶刺激。测定聚集情况以及细胞内cGMP和Ca2+水平。在一些实验中，还使用了一氧化氮活性抑制剂或增强剂来阐明松弛素的作用机制是否涉及L-精氨酸-一氧化氮途径。还对用松弛素处理和未处理的血小板进行了电子显微镜检查。
在用促聚集剂刺激之前，将血小板与松弛素预孵育会导致血小板聚集受到显著的、浓度依赖性抑制，同时血小板内cGMP升高，胞质Ca2+水平升高幅度降低。松弛素的作用似乎是通过一氧化氮介导的。在超微结构上，松弛素被证明可阻碍血小板聚集过程中通常发生的构象变化和颗粒胞吐作用。
松弛素这种新发现的抗聚集特性，连同此前研究中证明的该肽的血管舒张和降压活性，使这种激素可被视为预防妊娠血栓形成和高血压疾病以及心血管疾病的保护剂。
