Hypertension as a Maladaptive "Fight-or-Flight" Response?: Confirmatory Molecular Genetic Evidence From the Human Catecholamine Biosynthetic Pathway

The CURReNT DANISh MONICA RepORT ON hypeRTeNSION AND GeNeTIC VARIATION AT TyROSINe hyDROxyLASe Nearly 100 years ago, the great American physiologist Walter Bradford Cannon (1871–1945) coined the term “fight-orflight”,1 to refer to activation of the sympathetic branch of the autonomic nervous system in response to environmental threat. In the current issue of the American Journal of Hypertension, Nielsen and colleagues2 from Copenhagen, Denmark, utilize the longitudinal MONICA (MONItoring of trends and determinants in CArdiovascular disease, of the World Health Organization) cardiovascular cohort to provide convincing confirmatory evidence that links population basal BP to genetic variation in the rate-limiting point in catecholamine biosynthesis: tyrosine hydroxylase (TH). The Danish study demonstrated effects of the TH promoter variant C-824T (rs10770141) on both office and 24-h ambulatory blood pressure (BP), as well as the prevalence of hypertension. Coordinate effects of C-824T on heart rate as well as BP were consistent with an effect on sympathetic tone.