Enhanced baroreflex sensitivity in free-moving calponin knockout mice.
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.
Masuki
Shizue
S
Department of Sports Medicine, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Takeoka
Michiko
M
Taniguchi
Shun'Ichiro
S
Nose
Hiroshi
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D002339:Carotid Arteries / Q000294:innervation / Q000502:physiology; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009043:Motor Activity / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014851:Wakefulness; D000096985:Calponins
D000316:Adrenergic alpha-Agonists; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009599:Nitroprusside; D010656:Phenylephrine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000096985:Calponins