URINARY KALLIKREIN EXCRETION AND BLOOD-PRESSURE RESPONSE TO ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS AND CALCIUM-ANTAGONISTS IN HYPERTENSIVE PATIENTS

Objective: To investigate whether the hypotensive effects of angiotens in converting enzyme (ACE) inhibitors in comparison with those of calc ium antagonists might be predicted by urinary kallikrein activity, a m arker of the activity of the renal kallikrein-kinin system. Design: Se venty-five essential hypertensive patients were randomly assigned to t reatment with ACE inhibitors (enalapril or lisinopril 20 mg once a day ) or with calcium antagonists (nifedipine 20 mg twice a day or lacidip ine 4 mg once a day). Fifty-four had normal (NK) and 21 low (LK) kalli krein activity. Blood pressure was measured after 2 weeks, and 3 and 6 months. Patients whose diagnostic blood pressure, 2 weeks after the f irst dose, decreased by at least 15 mmHg or was less-than-or-equal-to 90 mmHg were defined as responders. The others were defined as non-res ponders. In non-responders a second drug was added and the patients we re not considered for further analysis. Methods: Urinary kallikrein ac tivity was determined by a spectrophotometric assay using a synthetic chromogenic substrate. Results: After 2 weeks therapy with ACE inhibit ors 88% of NK patients were responders, whereas in the LK subgroup 40% were responders, a significant difference between subgroups. For the patients treated with calcium antagonists, conversely, 59% of NK patie nts were responders in comparison with 82% of the LK subgroup, a signi ficant difference between drug groups. After 3 and 6 months of treatme nt blood pressure was significantly lower in NK patients treated with ACE inhibitors and in LK patients treated with calcium antagonists. In the NK group on ACE inhibitors the mean arterial pressure after the f irst dose was significantly related to that observed after 6 months (n = 0.71, P < 0.01). Conclusions. Our data indicate that urinary kallik rein activity may represent an index to predict the chronic antihypert ensive effect not only of ACE inhibition but also of calcium antagonis m, and support the concept that the renal kallikrein-kinin system migh t play some contributory role in modulating the hypotensive action of ACE inhibitors.