Our results show that mice with a double CathA/Scpep1 deficiency (DD mice) demonstrate hypertension, increased ET-1-induced vasoconstriction and prolonged half-life of circulating ET-1 as compared to both wild type (WT) animals and those with single CathA or Scpep1 deficiencies, strongly supporting this hypothesis. The gene discussed is SCPEP1; the disease is hypertensive disorder.