Enhanced baroreflex sensitivity in free-moving calponin knockout mice

Abstract

Masuki, Shizue, Michiko Takeoka, Shun'ichiro Taniguchi, and Hiroshi Nose. Enhanced baroreflex sensitivity in free-moving calponin knockout mice. Am J Physiol Heart Circ Physiol 284: H939-H946, 2003. First published November 14, 2002 10.1152/ajpheart.00610.2002Calponin 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 ϳ70% 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 (⌬HR) to spontaneous change in MAP (⌬MAP) varied in a wider range in KO mice with an 80% increase in the coefficient of variation for HR (P Ͻ 0.05), whereas MAP in KO mice was controlled in a narrow range similar to that in WT mice. The baroreflex sensitivity (⌬HR/ ⌬MAP), determined from the change in HR to the spontaneous change in MAP, was twofold higher in KO mice than that in WT mice (P Ͻ 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 Ͼ 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 Ͻ 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 ␣-adrenergic response of peripheral vessels to sympathetic nervous activity.carotid sinus denervation; heart rate variability CALPONIN, also called basic calponin or calponin H1, was first isolated from the chicken gizzard as an actinbinding protein, which was reported to be involved in the regulation of smooth muscle contraction (22). Calponin was reported to reduce unloaded isometric forces and shortening velocity (8,14,19,23) by the inhibition of actomyosin ATPase activity in a reconstituted isolated filament system (26). On the other hand, there have been several studies suggesting that calponin increases the contractile response to norepinephrine (NE) (18) or phenylephrine (PE) (9,16,20) by facilitating agonist-induced signal transduction.With the exception of these in vitro studies, however, there have been few studies investigating the role of cal...

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