Deficiency in the rate-limiting enzymes in the generation of S1P, sphingosine kinases (SphK) 1 and 2, resulted in a significant decrease in blood pressure as well as artery contractility in angiotensin II (AngII)-induced hypertension in the wild type (C57BL/6J) [68,70]. The gene discussed is AGT; the disease is hypertensive disorder.