Masuki Shizue, Takeoka Michiko, Taniguchi Shun'Ichiro, Nose Hiroshi
Department of Sports Medicine, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H939-46. doi: 10.1152/ajpheart.00610.2002. Epub 2002 Nov 14.
Calponin is an actin binding protein in vascular smooth muscle that modifies contractile responses. However, its role in mean arterial pressure (MAP) regulation has not been clarified. To assess this, MAP and heart rate (HR) were measured in calponin knockout (KO) mice, and the results were compared with those in wild-type (WT) mice. The measurements were performed every 100 ms during a 60-min free-moving state each day for 3 days. Mice in both groups rested during approximately 70% of the total measuring period. The mean HR during rest was significantly lower in KO mice than in WT mice but with no significant difference in MAP between the groups. The change in HR response (deltaHR) to spontaneous change in MAP (deltaMAP) varied in a wider range in KO mice with an 80% increase in the coefficient of variation for HR (P < 0.05), whereas MAP in KO mice was controlled in a narrow range similar to that in WT mice. The baroreflex sensitivity (deltaHR/deltaMAP), determined from the change in HR to the spontaneous change in MAP, was twofold higher in KO mice than that in WT mice (P < 0.01), whereas there were no significant differences in the baroreflex sensitivity determined by intravascular administration of phenylephrine and sodium nitroprusside between the two groups (P > 0.1). The MAP response to the administrated doses of phenylephrine in KO mice was reduced to one-half of that in WT mice (P < 0.01) but with no significant difference in the response to sodium nitroprusside between the groups. The differences in HR variability and the spontaneous baroreflex sensitivity between the two groups completely disappeared after carotid sinus denervation. These results suggest that the higher variability in HR for KO mice was caused by the increased spontaneous arterial baroreflex sensitivity, though not detected by the intra-arterial administration of the drug, and that the higher variability of HR may be a compensatory adaptation to the blunted alpha-adrenergic response of peripheral vessels to sympathetic nervous activity.
钙调蛋白是血管平滑肌中的一种肌动蛋白结合蛋白，可调节收缩反应。然而，其在平均动脉压（MAP）调节中的作用尚未明确。为了评估这一点，对钙调蛋白基因敲除（KO）小鼠的MAP和心率（HR）进行了测量，并将结果与野生型（WT）小鼠进行了比较。每天在60分钟的自由活动状态下，每100毫秒进行一次测量，持续3天。两组小鼠在大约70%的总测量时间内处于休息状态。KO小鼠休息时的平均心率显著低于WT小鼠，但两组之间MAP无显著差异。KO小鼠中HR反应（deltaHR）对MAP自发变化（deltaMAP）的变化范围更广，HR变异系数增加了80%（P<0.05），而KO小鼠的MAP被控制在与WT小鼠相似的狭窄范围内。由HR对MAP自发变化的变化确定的压力反射敏感性（deltaHR/deltaMAP），KO小鼠比WT小鼠高两倍（P<0.01），而两组之间通过血管内注射去氧肾上腺素和硝普钠确定的压力反射敏感性无显著差异（P>0.1）。KO小鼠对给予剂量的去氧肾上腺素的MAP反应降低至WT小鼠的一半（P<0.01），但两组之间对硝普钠的反应无显著差异。两组之间HR变异性和自发压力反射敏感性的差异在颈动脉窦去神经支配后完全消失。这些结果表明，KO小鼠HR的较高变异性是由自发动脉压力反射敏感性增加引起的，尽管通过动脉内给药未检测到，并且HR的较高变异性可能是对外周血管对交感神经活动的α-肾上腺素能反应减弱的一种代偿性适应。
