Gain-of-function mutations in the gene encoding phosphodiesterase (PDE) 3A cause hypertension with brachydactyly (HTNB). If the hypertension is not treated, the patients die of stroke by the age of 50 years. Even treated, the blood pressure does not reach physiological levels. Surprisingly, despite the decade-long hypertension, HTNB patients do not show cardiac damage. The presentation comprises an introduction of HTNB and will show analyses of HTNB rat and cell-based models, which suggest mechanisms accounting for the cardioprotection of the mutations.