ANTIHYPERTENSIVE EFFICACY OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITIONAND ASPIRIN COUNTERACTION

Objective: Blockade of bradykinin breakdown and enhancement of prostag landin release probably participate in the antihypertensive activity o f angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase block ers may attenuate the efficacy of ACE inhibitors by interfering with p rostaglandin synthesis, and patients taking aspirin may not benefit fr om ACE inhibition. This study was designed to evaluate the incidence o f the counteractive phenomenon and to define minimal aspirin dosage th at causes an antagonistic effect. Methods: These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe u ntreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in gro up 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenu ation of more than 20% of the mean blood pressure decrease produced by enalapril, was the criteria that defined antagonism. Results: The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: m ean arterial pressure was lowered by 63% and 91% less, respectively. R esults were independent of the drug administration order. In ''respond ers,'' aspirin significantly attenuated the renin rise associated with ACE inhibition. Conclusions: These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardle ss of hypertension severity. Antagonism may be mediated through prosta glandin inhibition according to predominance, in an individual patient , of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.