We investigated the vasomotor effects of sorafenib, a widely used multikinase inhibitor in the treatment of hepatocellular and renal cell carcinoma and tested the hypothesis that sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, could represent a pharmacological strategy for the treatment of TKI-induced hypertension. The gene discussed is PDE5A; the disease is hereditary clear cell renal cell carcinoma.