TRANDOLAPRIL IS DEESTERIFIED TO THE DIACID METABOLITE, TRANDOLAPRILAT, WHICH IS APPROXIMATELY EIGHT TIMES MORE ACTIVE AS AN INHIBITOR OF ACE ACTIVITY. ACE IS A PEPTIDYL DIPEPTIDASE THAT CATALYZES THE CONVERSION OF ANGIOTENSIN I TO THE VASOCONSTRICTOR, ANGIOTENSIN II. ANGIOTENSIN II IS A POTENT PERIPHERAL VASOCONSTRICTOR THAT ALSO STIMULATES SECRETION OF ALDOSTERONE BY THE ADRENAL CORTEX AND PROVIDES NEGATIVE FEEDBACK FOR RENIN SECRETION. THE EFFECT OF TRANDOLAPRIL IN HYPERTENSION APPEARS TO RESULT PRIMARILY FROM THE INHIBITION OF CIRCULATING AND TISSUE ACE ACTIVITY THEREBY REDUCING ANGIOTENSIN II FORMATION, DECREASING VASOCONSTRICTION, DECREASING ALDOSTERONE SECRETION, AND INCREASING PLASMA RENIN. DECREASED ALDOSTERONE SECRETION LEADS TO DIURESIS, NATRIURESIS, AND A SMALL INCREASE OF SERUM POTASSIUM.