Impaired arterial pressure regulation during exercise due to enhanced muscular vasodilatation in calponin knockout mice.

摘要

Calponin is known to be an actin binding protein in smooth muscle, inhibiting actomyosin ATPase activity in vitro. We previously reported that alpha-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 mice was enhanced at rest. In the present study, we assessed arterial pressure regulation in WT and KO mice during graded treadmill exercise at 5, 10, and 15 m min-1. Mean arterial pressure (MAP) in KO mice fluctuated more than that in WT mice at every speed of exercise with two-fold higher variances (P < 0.001). The baroreflex sensitivity (Delta HR/Delta MAP) in WT mice (n = 6), determined from the heart rate response (Delta HR) to spontaneous change in MAP (Delta MAP), was -5.1 +/- 0.6 beats min-1 mmHg-1 (mean +/- S.E.M.) at rest and remained unchanged at -5.0 +/- 0.9 beats min-1 mmHg-1 during exercise (P < 0.01), while that in KO mice (n = 6) was -9.9 +/- 1.7 beats min-1 mmHg-1 at rest, significantly higher than that in WT mice (P < 0.001), and was reduced to -4.7 +/- 0.4 beats min-1 mmHg-1 during exercise (P < 0.01), not significantly different from that in WT mice. 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) mice. 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 s in KO mice, shorter than 5.8 +/- 0.6 s in WT mice (P < 0.001). Prior administration of alpha-adrenergic blockade (phentolamine) shortened the time in WT mice to that in KO mice (P < 0.001), but did not shorten the time in KO mice. Thus, impaired MAP regulation in KO mice during exercise was caused by a blunted muscle vascular alpha-adrenergic contractile response and by the attenuated HR response to spontaneous change in MAP due to reduced baroreflex sensitivity.