“Diabetes mellitus is a leading cause of renal disease [a disease of the kidney] and an independent risk factor for cardiovascular disease complications in the United States. Accumulating evidence suggests that serotonin [5-hydroxytryptamine (5-HT)], a well-known mitogen and a potent vasoconstrictor, may also stimulate pathological processes in diabetes. 5-HT has been associated with cardiovascular diseases such as atherosclerosis and pulmonary hypertension, but it has been overlooked in some diseases because of its low circulating physiological levels (estimated to be in the 10−9M range) and a lack of understanding of the roles of 5-HT in the peripheral systems. One way by which physiological levels of 5-HT may have an effect on vascular tone is through the interaction with other vasoactive substances including ET-1 [endothelin-1], which could exacerbate the pathophysiological mechanisms….
We tested the hypothesis that the interaction between 5-HT and ET-1 in VSMC [vascular smooth muscle cells, which line the inner surface of blood vessels] at physiological concentrations would cause enhanced activation of both p42/44 MAPK [mitogen-activated protein kinase] and JAK2 [Janus kinase 2] signaling pathways in vitro for acute preincubations of the cultured VSMCs with 5-HT and/or ET-1 that could contribute to altered cellular functions especially in hyperglycemic conditions. We also hypothesized that the physiological levels of 5-HT and ET-1 interact to stimulate an increase in the contractile response in arteriesex vivo that may lead to altered vascular functions that may contribute to early development of cardiovascular injury as a consequence of diabetes.”