Natriuretic Peptides as Cardiovascular Safety Biomarkers in XXXX : Comparison With Blood Pressure, Heart Rate, and Heart Weight.

@entity1 @entity296 @entity137 @entity101 @entity44805 @entity2240 @entity908 @entity1283 @entity35412 @entity1955 @entity5491 @entity594 @entity35 @entity551 @entity6462
UNASSIGNED: Cardiovascular (CV) @entity137 is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV @entity137 during preclinical development and prioritize compounds at lower risk of causing such @entity137 . Evidence of @entity296 can be detected by measuring concentrations of biomarkers such as @entity35412 and @entity908 kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to @entity1283 and @entity296 in animals, and major adverse cardiovascular events (MACE) in @entity1 . Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in @entity1 . Their utility as biomarkers of CV function and @entity137 in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in @entity35 administered compounds that caused @entity551 or @entity101 , including @entity594 , @entity44805 , @entity5491 , @entity6462 , @entity1955 , or @entity2240 for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and @entity1283 in short-duration @entity35 studies.
