Influence of 5-hydroxytryptamine on aortic valve competence in vitro

Background and aint of the study: The contraction of cusp tissue has been i mplicated to play a role in aortic valve function. The effect of the contra ctile agent 5-hydroxytryptamine (5-HT) on the competence of isolated aortic roots has been assessed, and the vasomotor properties of 5-HT on aortic ro ot tissue examined. Methods. Isolated porcine aortic roots were pressurized with Kreb's solutio n through the aortic arch. 5-HT was added in increasing concentrations (10( -7) to 10(-5)M) and the degree of leakage measured over time. In additional experiments, portions of sinotubular junction, sinus, annular and cusp tis sue were set up in organ baths, placed under tension, and challenged with 5 -HT (10(-9) to 10(-5)M). Viability of each valve structure was assessed by addition of KCl (90 mM). Results: The rate of leakage from intact aortic roots increased when 10(-6) and 10(-5)M 5-HT was added. The maximum effect, observed at 10(-5)M 5-HT, was equal to an increase of 61.8 +/- 23.0% above control (p <0.05). The per fusion pressure at each concentration of 5-HT was unchanged. This response was inhibited by the 5-HT2A receptor antagonist ketanserin. Addition of KCl to isolated valve structures gave a mean contractile response of 0.8 +/- 0 .1mN for cusp, 19 +/- 11.0 mN for annular, 29 +/- 8.0mN for sinus, and 23 /- 8.0mN for sinotubular junction tissue (each n = 4). Only cusp tissue con tracted when treated with 5-HT, with a maximum 105.5 +/- 17.2% (n = 4) of t he response to KCl. The response to 5-HT was blocked by the 5-HT2A-receptor antagonist ketanserin at 10(-6)M (n = 4). None of the other aortic root st ructures responded to 5-HT. Conclusion: These results show that 5-HT influences the competence of isola ted porcine aortic valves. This effect is contributed by contraction of the cusp tissue, and is mediated by 5-HT2A receptors. These effects may contri bute to the association between valve dysfunction, 5-HT and certain appetit e suppressants.