Adrenergic and Serotonergic Synergism in the Mouse Thoracic Aorta

Ali, Z., McGrath, J.C. and Daly, C.J. (2004) Adrenergic and Serotonergic Synergism in the Mouse Thoracic Aorta. University of Glasgow 2004, 2004.

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The vasoactive nature of 5-hydroxytryptamine (5-HT) and its involvement in synergy is well-studied. Stupecky et al. (1986) discussed synergistic interactions of α1-adrenergic and serotonergic contractions in the rabbit aorta by using single equi-effective concentrations of agonists producing a response of 0.1g Force, passing the contractile ′threshold stimulus′.Synergism was demonstrated where combinations of these agonists concentrations produced responses of 0.5g to 2.7g Force. Agonist synergy is also indicated from the sensitivity of the concentration response curve (CRC). We have investigated synergy between 5-HT and α-AR mediated contractions in the mouse aorta. 4 month old male (3040g) 129/Sv/C57BL/6J mice were euthanased by CO2 and their aortae isolated. 2mm rings were mounted on wire myographs in Krebs at 37°C. After an initial challenge to 125mM KCl, the endothelium was tested with 30µM ACh (10µM phenylephrine/ PE precontraction). Cumulative CRCs (1nM-300µM) were constructed to PE or 5-HT in the absence or presence of 10 or 30nM 5-HT or PE respectively. Maximum responses and logEC50 values were compared using a one-way ANOVA with a Bonferroni post-test.The maximum response to PE (Mean ± S.E.M., 0.97 ± 0.06g) was unaffected by 10nM (1.00 ± 0.12g) or 30nM 5-HT (1.01 ± 0.07g). Similarly, the maximum 5-HT response (1.33 ± 0.10g) was unaffected by 10nM (1.53 ± 0.18g) or 30nM PE (1.12 ± 0.09g). 10nM 5-HT or PE had no effect on PE or 5-HT sensitivity respectively. However 30nM 5-HT caused a 6-fold increase in sensitivity to PE whilst 30nM PE resulted in 5-HT sensitivity being increased 3-fold (Table 1).In our preparation 10nM PE or 5-HT was a sub-threshold concentration for contraction, whilst 30nM PE or 5-HT was sufficient to cause a contraction (i.e. over the threshold stimulus). Addition of the agonist on top of this supra-threshold concentration resulted in an enhanced response. We have demonstrated there needs to be an increased tone as a result of the PE or 5-HT treatment before synergy can be observed. Thus our results agree with Stupecky et al. (1986). Furthermore, the small 6-fold and 3-fold increases in sensitivity are likely to be a result of ″mutual effect amplification″ described by Leff′s (1987) mathematical model of synergy. In conclusion, serotonergic and α1-adrenergic synergy has now been demonstrated in the mouse thoracic aorta.

Item Type:Conference or Workshop Item
Additional Information:Communication.
Glasgow Author(s) Enlighten ID:Daly, Professor Craig and McGrath, Professor John
Authors: Ali, Z., McGrath, J.C., and Daly, C.J.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences

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