Eur J Clin Pharmacol (1983) 24:579-583 European Journal of Clinical Pharmacology © Springer-Verlag 1983 Effect of Indapamide on the Baroreceptor Reflex in Essential Hypertension R. Carretta, B. Fabris, L. Tonutti, G. Bellini, G. Battilana, A. Bianchetti 1, and L. Campanacci Istituto di Patologia Medica, University of Trieste and 1Serviziodi Anestesia, Ospedale Maggiore, Trieste, Italy Summary. The effect of chronic treatment with in- dapamide on blood pressure (BP), baroreceptor sen- sitivity (BRS) and vascular reactivity (VR) were in- vestigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135 _+ 6 to 112 + 2 mmHg (p < 0.001); the heart rate (HR) had not changed, VR had decreased from 6.1_+1.2 to 4.8_+l.8(pg-min.kg) -1 (p<0.05), and BRS had increased from 8.3 + 3.7 to 12.2+ 5.3 ms/ mmHg (p < 0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r= 0.59; p < 0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations. Key words: indapamide, hypertension; baroreflex, vascular reactivity, heart rate, blood pressure change Indapamide is a new anti-hypertensive drug, usually classified as a diuretic [1]. However, in an effective anti-hypertensive dose of 2.5 mg daily, the drug has only a minimal diuretic effect [2]. Its hypotensive action appears to be related to re- duction in the vascular reactivity to pressor agents, as shown during studies in vivo [3, 4] and in isolated preparations of blood vessel [5, 6]. Although its hy- potensive effect is probably dependent on its vascu- lar action, the heart rate does not change [2, 7, 8], which suggests, amongst other possibilities, addi- tional effect on the baroreceptor reflex. The aim of the present study was to determine whether the absence of tachycardia after chronic treatment with indapamide could be due to the inter- ference by the drug with the baroreceptor reflex. For this purpose the baroreflex arc function was quanti- tatively assessed, as the degree of bradycardia in re- sponse to acute phenylephrine-induced hyperten- sion in a series of patients with essential hyperten- sion, during both placebo and successful chronic treatment with indapamide. Patients and Methods The study was carried out in 10 patients (7 males and 3 females) with uncomplicated essential hyperten- sion. The average age of the group was 42_+ 5 years (mean-+SEM; range 31 to 56years). All patients were carefully examined and investigations were done to exclude secondary causes of hypertension. Every subject had a mean arterial pressure (MAP), defined as the diastolic blood pressure plus ½ pulse pressure, of at least 105 mmHg when measured in the Outpatient Clinic. None of the patients took anti- hypertensive therapy for at least one month before the study. Procedures In random order, each subject was placed for 3 months either on oral placebo or on oral indapa- mide alone as a single daily dose of 2.5 mg. Every subject completed both the placebo and the indapa- mide phases of the study, and so each acted as his own control. At the end of each 3 month period, the investigations mentioned below were performed in