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 angiotensin converting enzyme (ACE) inhibitors in comparison with those of calcium antagonists might be predicted by urinary kallikrein activity, a marker of the activity of the renal kallikrein—kinin system. Design: Seventy-five essential hypertensive patients were randomly assigned to treatment with ACE inhibitors (enalapril or lisinopril 20 mg once a day) or with calcium antagonists (nifedipine 20 mg twice a day or lacidipine 4 mg once a day). Fifty-four had normal (NK) and 21 low (LK) kallikrein activity. Blood pressure was measured after 2 weeks, and 3 and 6 months. Patients whose diagnostic blood pressure, 2 weeks after the first dose, decreased by at least 15mmHg or was ≤ 90mmHg were defined as responders. The others were defined as non-responders. In non-responders a second drug was added and the patients were not considered for further analysis. Methods: Urinary kallikrein activity was determined by a spectrophotometric assay using a synthetic chromogenic substrate. Results: After 2 weeks therapy with ACE inhibitors 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 patients were responders in comparison with 82% of the LK subgroup, a significant difference between drug groups. After 3 and 6 months of treatment 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 first dose was significantly related to that observed after 6 months (n = 0.71, P <0.01). Conclusions: Our data indicate that urinary kallikrein activity may represent an index to predict the chronic antihypertensive effect not only of ACE inhibition but also of calcium antagonism, and support the concept that the renal kallikrein—kinin system might play some contributory role in modulating the hypotensive action of ACE inhibitors.