Background: Agonist-mediated sensitisation of myofilaments to calcium is known to play a role in the regulation of vascular tone in human myometrial arteries during pregnancy (Wareing et al. 2005). Pregnancy complications such as intrauterine growth restriction and pre-eclampsia are known to involve alterations in vasoreactivity of myometrial arteries to constrictive agents such as the thromboxane mimetic U46619 and arginine vasopressin (AVP). Understanding the mechanisms by which these molecules act to regulate tone of human arteries in normal pregnancy will therefore be of importance in elucidating changes accompanying the above complications that result in elevated vascular resistance. Aims: To assess the level of agonist-dependent sensitisation of tone to sub-maximal activating calcium in permeabilised myometrial arteries using a selection of vasoactive agonists known to be present in the circulation: U46619, AVP and sphingosine-1-phosphate (S1P). Methods: Arteries were dissected from biopsies obtained during Caesarean section, following written informed consent, and mounted in a wire myograph. Agonist-induced constriction (to 10µM S1P, 1µM U46619 and 10nM AVP) was assessed in vessels permeabilised with α-toxin and already sub-maximally constricted with pCa6.7 solution by ~30% (relative to a previous constriction to pCa4.5 solution). The involvement of rho-associated kinase (ROK) in any agonist-mediated sensitisation of tone to pCa6.7 was established using the inhibitor Y27632 (10µM). Results: U46619 (N=5) or AVP (N=4), added to pCa6.7 solution, produced constrictions over and above that of pCa6.7 alone; these were of similar magnitude to preceding constrictions to pCa4.5 alone (1.1 ±0.2 and 0.9 ±0.3 fold of that to pCa 4.5 respectively). S1P (N=5), however, produced a far smaller constriction (0.3 ±0.2 fold change compared to pCa 4.5). The constriction to U46619 was reduced to 17% of maximal constriction, that of AVP to 40% and that of S1P to 12% in the presence of Y27632. Conclusion: Interestingly, receptor-mediated Ca2+-sensitisation of human arterial tone, at least at pCa6.7, is agonist-dependent. Irrespectively, ROK inhibition substantially reduced the sensitisation to U46619, AVP or S1P. These data indicate that vasoactive agents may induce constrictions by evoking different magnitudes of Ca2+-sensitisation, a finding of importance when considering potential mechanisms by which circulatory agents promote increased vascular resistance associated with hypertensive disorders e.g. for pregnancy, pre-eclampsia or IUGR.