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Cardiovascular responses to single stressors diminish over time. Interaction of different stressors influencing hemodynamic variables, indicative of stress-induced reactivity and physiological responses are, however, poorly understood. We investigated time course of mental (using mental arithmetic, MA) and orthostatic (using head up tilt, HUT) challenges induced responses in 16 males. Three protocols were used: HUT, MA and MA+HUT, with sessions randomized and two weeks apart. Hemodynamic responses were compared for 30s epochs of stress application (stress(T1), stress(T2)...). Compared to baseline, HUT, HUT+MA and MA applications affected heart rate (HR) (+15.1+/-8.0 bpm, +20.0+/-9.2 bpm, +11.9+/-7.2 bpm, all p's<.001, respectively) and stroke volume (SV) (-22.3+/-8.1 ml, -22.0+/-10.4 ml, -7.6+/-8.7 ml, all p's<.001, respectively). HUT and MA+HUT induced HR increases were higher in stress(T2) compared to stress(T1) (p<.05) and reached maximum at stress(T2). HUT and MA+HUT further reduced SV in stress(T2) as compared to stress(T1) (p<.001); lowest SV was in stress(T2). Mean arterial pressure reached its minimum in stress(T1) during HUT and MA+HUT (-6.0+/-8.5mm Hg, p<.001, -4.4+/-9.7 mm Hg, p<.01, respectively) but increased in MA (+4.3+/-3.7 mm Hg, p<.01). Combination of MA+HUT resulted in different time courses of blood pressure responses as compared to HUT alone. We conclude that application of single or combined stress challenges lead to stressor- and time dependent-initial changes in cardiovascular responses. Our findings provide novel insights regarding the duration a stressor must be applied to elicit maximal cardiovascular responses.