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Recently, this single-parameter model has been argued not to provide a realistic representation of pressure�Cvelocity or pressure�Cflow relationships of the cerebral circulation (Panerai, 2003). For example, measures of arterial blood pressure do not directly reflect cerebral perfusion pressure because intracranial pressure also influences cerebral perfusion pressure (Panerai, 2003). In addition, arterial partial pressure of CO2, intrathoracic pressure and cerebral autoregulation can all influence cerebral vascular tone (Panerai, 2003). Moreover, the brain vascular bed is small, and cerebral blood flow is strongly influenced by changes in cardiac output independently of changes in blood pressure (Ogoh et al. 2005). Therefore, Panerai (2003) has suggested that the calculation of cerebral vascular resistance or conductance is a ��black-box�� model parameter, [http://en.wikipedia.org/wiki/ALG1 ALG1] lacking in physiological specificity and difficult to measure with acceptable accuracy. An alternative approach [http://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html learn more] is the calculation of CCP, which has been found to be useful in the assessment of the dynamics of the cerebral circulation (Richards et al. 1999) and as an index of cerebral vascular tone (Panerai et al. 1995, 1999; Czosnyka et al. 1999; Richards et al. 1999; Weyland et al. 2000; Aaslid et al. 2003; Ogoh et al. 2010). Indeed, in our previous study we observed that moderate-intensity single-leg kicking exercise significantly increased brain CCP in young subjects, although cerebral vascular resistance was unchanged (Ogoh et al. 2010). In the present study, the response of CCP to large-muscle-mass dynamic leg cycling exercise also differed from that of CVCi (Table 1 and Figs 2 and 3). Although the CCP progressively increased from rest to both low- and moderate-intensity cycling in both age groups, a decrease in CVCi was observed only during moderate-intensity [http://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html Cobimetinib] exercise in the older subjects. Overall, these findings suggest that measures of resistance or conductance alone may underestimate the response of the cerebral vasculature to exercise. Nevertheless, both measures indicate that ageing is associated with a greater exercise-induced increase in cerebral vascular tone. Although the exact mechanism underlying the significantly greater increase in CCP during exercise in older subjects is not clear, several possibilities warrant discussion. The arterial partial pressure of CO2 is a powerful controller of the cerebral vasculature (Aaslid et al. 1989; Garnham et al. 1999; Panerai et al. 1999) and has been shown to be strongly related to CCP (Garnham et al. 1999; Panerai et al. 1999; Richards et al. 1999; Weyland et al. 2000). Moreover, exercise-induced increases in CCP have previously been observed to be related to decreases in the (Ogoh et al. 2010).