Key Points
- To evaluate the acute and chronic pharmacodynamic effects of enalapril on serum angiotensin converting enzyme activity and blood pressure in patients with essential hypertension.
- Conducted a double-blind randomized trial administering a single 10 mg oral enalapril dose to 12 hypertensive subjects to evaluate acute effects over 24 hours.
- Titrated enalapril from 5 mg to 20 mg twice daily in 11 patients for 3 to 12 months to achieve diastolic blood pressure below 90 mmHg.
- Measured serum concentrations of the active metabolite MK422 (enalaprilic acid), serum ACE inhibition, and blood pressure responses across acute and chronic phases.
- Acute enalapril administration achieved peak blood pressure reduction at 6 hours lasting 24 hours, with strong correlations between drug levels and ACE inhibition (r = 0.98, P < 0.001, n = 16) and ACE inhibition and hypotensive effect (r = 0.84, P < 0.001, n = 16).
- Chronic therapy demonstrated correlations between serum MK422 and ACE inhibition (r = 0.8, P < 0.001, n = 104), and blood pressure reductions correlated with both MK422 (r = 0.37, P < 0.05, n = 39) and ACE inhibition (r = 0.45, P < 0.01, n = 42).
- The drug concentration-response curve shifted rightward during chronic treatment, with the ID50 for serum ACE increasing from 32 ng/ml acutely to 70 ng/ml chronically, suggesting enzyme induction.
Structured PICO
Does enalapril reduce blood pressure and inhibit ACE in subjects with essential hypertension?
PPopulationSubjects with essential hypertension (n=12 in acute study, n=11 in chronic study)
IInterventionEnalapril (acute: 10 mg oral single dose; chronic: titrated 5 to 20 mg twice a day for 3-12 months)
OOutcomeBlood pressure, serum MK422 (enalaprilic acid) levels, and serum angiotensin converting enzyme (ACE) inhibitionsurrogate
Chronic enalapril therapy induces ACE, requiring higher drug levels to achieve the same degree of ACE inhibition compared to acute administration, though blood pressure reduction remains similar.