S100B modulates the hemodynamic response to norepinephrine stimulation.
BACKGROUND
We have previously reported that S100B acts as an intrinsic negative regulator of the myocardial hypertrophic response to norepinephrine (NE).


METHODS
To examine the role of S100B in acute and chronic hemodynamic responses to NE stimulation, knockout (KO) mice devoid of the S100B gene, transgenic (TG) mice with forced overexpression of S100B, and control CD1 mice were injected subcutaneously once daily with NE (1.5 mg/kg) or vehicle for 28 days.


RESULTS
The acute and chronic hemodynamic responses were not different in CD1 and TG mice. In KO mice, both the chronic and acute increase in blood pressure (BP) in response to NE was attenuated compared with CD1 mice. NE induced ventricular myocyte hypertrophy and smooth muscle proliferation in CD1 mice, responses that were augmented in KO mice. In TG mice, NE did not induce myocyte hypertrophy or smooth muscle cell proliferation. NE treatment of smooth muscle cells derived from KO mice resulted in lower cytosolic calcium concentrations compared to CD1 and TG mice. NE induced S100B in ventricular myocytes and increased S100B in arterial tissues of CD1 and TG mice. The giant phosphoprotein AHNAK is expressed in both ventricular myocytes and aortic smooth muscle cells (ASMCs). In response to NE, S100B co-immunoprecipitates with AHNAK in ventricular myocytes and ASMCs.


CONCLUSIONS
Thus, absence of S100B is associated with attenuation of the hemodynamic response to catecholamines, in contradistinction to, the augmented cardiac hypertrophy and smooth muscle cell proliferation.
Tsoporis
James N
JN
Division of Cardiology, Department of Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Overgaard
Christopher B
CB
Izhar
Shehla
S
Parker
Thomas G
TG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*
C489572:Ahnak protein, mouse; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; D002118:Calcium; D009638:Norepinephrine