Calponin is known to be an actin binding protein in smooth muscle, inhibiting actomyosin ATPase activity in vitro. We previously reported that -adrenergic vasoconstriction in calponin knockout (KO) mice was reduced compared with that in wild-type C57BL/6J (WT) mice and, as a compensation, arterial baroreflex sensitivity in KO was enhanced at rest (Masuki et al. 2003). In the present study, we assessed arterial pressure regulation in WT and KO during graded treadmill exercise at 5, 10, and 15 m/min. Mean arterial pressure (MAP) in KO fluctuated more than that in WT at every speed of exercise with two-fold higher variances (P<0.001). The baroreflex sensitivity (HR/& [Delta]MAP) in WT (n=6), determined from the heart rate response (HR) to spontaneous change in MAP (& [Delta]MAP), was -5.1±0.6 (SE) beats/min/mmHg at rest remained unchanged at -5.0±0.9 beats/min/mmHg during exercise (P<0.01), while that in KO (n=6) was -9.9±1.7 beats/min/mmHg at rest, significantly higher than that in WT (P<0.001), was reduced to -4.7±0.4 beats/min/mmHg during exercise (P<0.01), not significantly different from that in WT. In another experiment, we measured muscle blood flow (MBF) in the thigh by Laser Doppler flowmetry, electromyogram (EMG), and MAP during voluntary locomotion in KO (n=7) and WT (n=7). Muscle vascular conductance, MBF/MAP, started to increase immediately after locomotion, judged from EMG, and reached 50% of the maximum after the time of 2.3±0.2 sec in KO, shorter than 5.8±0.6 sec in WT (P<0.001). Prior administration of -adrenergic blockade (phentolamine) shortened the time in WT to that in KO (P<0.001), but did not shorten the time in KO. Thus, impaired MAP regulation in KO during exercise was caused by a blunted muscle vascular -adrenergic contractile response and by the attenuated HR response to spontaneous change in MAP due to reduced baroreflex sensitivity.