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¹ Departments of Physiology & Biophysics and Clinical Neurosciences, Faculty of Medicine and Faculty of Kinesiology, University of Calgary, 3330 Hospital Drive NW, Calgary Alberta, T2N 4 N1 Canada
² Department of Orthopaedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, USA

The relative importance of CO₂ and sympathetic stimulation in the regulation of cerebral and peripheral vasculatures has not been previously studied in humans. We investigated the effect of sympathetic activation, produced by isometric handgrip (HG) exercise, on cerebral and femoral vasculatures during periods of isocapnia and hypercapnia. In 14 healthy males (28.1 ± 3.7 (mean ± S.D.) years), we measured flow velocity (; transcranial Doppler ultrasound) in the middle cerebral artery during euoxic isocapnia (ISO, +1 mmHg above rest) and two levels of euoxic hypercapnia (HC5, end-tidal P_CO2, P_ET,CO2, = +5 mmHg above ISO; HC10, P_ET,CO2 = +10 above ISO). Each P_ET,CO2 level was maintained for 10 min using the dynamic end-tidal forcing technique, during which increases in sympathetic activity were elicited by a 2-min HG at 30% of maximal voluntary contraction. Femoral blood flow (FBF; Doppler ultrasound), muscle sympathetic nerve activity (MSNA; microneurography) and mean arterial pressure (MAP; Portapres) were also measured. Hypercapnia increased and FBF by 5.0 and 0.6% mmHg^–1, respectively, and MSNA by 20–220%. Isometric HG increased MSNA by 50% and MAP by 20%, with no differences between ISO, HC5 and HC10. During the ISO HG there was an increase in cerebral vascular resistance (CVR; 20 ± 11%), while remained unchanged. During HC5 and HC10 HG, increased (13% and 14%, respectively), but CVR was unchanged. In contrast, HG-induced sympathetic stimulation increased femoral vascular resistance (FVR) during ISO, HC5 and HC10 (17–41%), while there was a general decrease in FBF below ISO. The HG-induced increases in MSNA were associated with increases in FVR in all conditions (r = 0.76–0.87), whereas increases in MSNA were associated with increases in CVR only during ISO (r = 0.91). In summary, in the absence of hypercapnia, HG exercise caused cerebral vasoconstriction, myogenically and/or neurally, which was reflected by increases in CVR and a maintained . In contrast, HG increased FVR during conditions of ISO, HC5 and HC10. Therefore, the cerebral circulation is more responsive to alterations in P_CO2, and less responsive to sympathetic stimulation than the femoral circulation.

(Received 23 March 2005; accepted after revision 11 May 2005; first published online 12 May 2005)
Corresponding author M. J. Poulin: Department of Physiology & Biophysics, Faculty of Medicine, University of Calgary, Heritage Medical Research Building Room 212, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.  Email: poulin{at}ucalgary.ca

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