EFFECT OF LOW-DOSE ASPIRIN ON THROMBOXANE PRODUCTION AND THE ANTIHYPERTENSIVE EFFECT OF CAPTOPRIL

Some of the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is through decreased kinin degradation, leading to enhanc ed production of vasodilator arachidonic acid metabolites. It was reas oned that if ACE inhibition also leads to an increase in the productio n of the potent vasoconstrictor thromboxane A2, then maneuvers that se lectively inhibit thromboxane production without reducing prostaglandi ns (PG) E2 + PGI2 might enhance the antihypertensive effect of ACE inh ibition. This double-blinded, randomized, crossover study was therefor e undertaken to determine: (1) if captopril increases platelet and/or renal thromboxane production; and (2) if low-dose aspirin enhances the antihypertensive effect of captopril. Patients with mild essential hy pertension and no other significant medical problems were studied. In a double-blinded, random order, patients took captopril alone (25 mg e very 12 h) for 2 wk and captopril plus aspirin (75 mg/day) for another 2 wk. Active treatment periods were preceded by 2 wk of single-blind placebo. Fifteen patients with a mean age of 53 yr and an average mean arterial pressure (MAP) of 114 +/- 8 (+/-SD) mm Hg were studied. Seru m thromboxane B2 was higher (P < 0.05) during treatment with captopril /placebo (600 +/- 46 (+/-SE) pg/mL) than during the two washout period s combined (420 +/- 57 and 553 +/- 78) and was lowest (P < 0.0005) dur ing treatment with captopril/aspirin (302 +/- 36). Captopril treatment significantly increased the urinary excretion of PGE2 (P = 0.038). Ca ptopril/placebo significantly lowered MAP (P < 0.05) to 105.0 +/- 3.7 mm Hg compared with the washout period. However, the addition of aspir in to captopril caused no additional lowering of MAP (105.2 +/- 2.8 mm Hg). It was concluded that treatment with captopril does increase pla telet thromboxane production. However, lowering platelet thromboxane w ith low doses of aspirin may not enhance the antihypertensive effect o f captopril.