CaMK4 gene deletion induces hypertension

Background--the expression of calcium/calmodulin-dependent kinase iv (camkiv) was hitherto thought to be confined to the nervous system. however,a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human camkiv gene (camk4),which suggests a role for this kinase in the regulation of vascular tone. methods and results--to directly assess the role of camkiv in hypertension,we characterized the cardiovascular phenotype of camk4 mice. they displayed a typical hypertensive phenotype,including high blood pressure levels,cardiac hypertrophy,vascular and kidney damage,and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. interestingly,in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. eventually,in a population study,we found that the rs10491334 variant associates with a reduction in the expression levels of camkiv in lymphocytes from hypertensive patients. conclusions--taken together,our results provide evidence that camkiv plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. © 2012 the authors.