Relaxin, best known for its reproductive effects can be also viewed as a cardiovascular hormone. Its action includes
a marked increase in coronary blood flow, exerted through the up-regulation of inducible nitric oxide (NO) synthase
(NOS II) and NO production in vascular endothelial and smooth muscle cells. This effect seems to involve NF-B, a
classical transcription factor controlling NOS II induction by proinflammatory cytokines. The present study was designed
to clarify the mechanisms underlying the relaxin-induced up-regulation of NOS II gene in endothelial cells. Rat coronary
endothelial (RCE) cells were grown for 30 min, 2, 6 and 12 h in the absence or presence of 60 ng/ml porcine relaxin.
Time-course analysis of the expression of NOS II and the proinflammatory cytokines IL-1 and TNF was performed.
Relaxin induced the expression of NOS II transcript and protein at all these time points. No correlation was observed
with the expression profiles of the genes for the assayed cytokines: IL-1 expression showed a first peak at 30 min.
followed by a decline and a second peak at 12 h, whereas faint TNF- expression was only detected at 2 h. Relaxin retained
the ability to induce NOS II transcript and to generate NO even in the presence of neutralizing anti- IL1 and/or
anti-TNF- antibodies. The current findings suggest that the induction of NOS II by relaxin in coronary endothelial cells
is a direct effect of this hormone and does not depend on a primary cytokine-mediated pathway that eventually results in
NF-B activation and NOS II induction.