Significance of vascular remodeling and vagosympathetic tone in the implementation of the antihypertensive effect of indapamide retard

Background. There are opinions about various mechanisms of antihypertensive action of indapamide, including modulation of the neurohumoral status and vasodilating effect, which are of interest for evaluating its effectiveness depending on vagosympathetic tone and the severity of vascular remodeling in patients with arterial hypertension (AH).

Objective. Evaluation of the effectiveness of indapamide retard depending on the presence of vascular remodeling and heart rate variability (HRV) in uncomplicated essential hypertension.

Methods. The study involved 75 patients (43 men and 32 women) aged 48 to 60 years (mean age 56.3±6.4 years) with AH I-II degree. Doppler echocardiography, Doppler ultrasound of the brachial artery (BA), 24-hour blood pressure monitoring, and ECG Holter monitoring were performed. The dynamics of BA wall remodeling parameters, endothelium-dependent vasodilation (EDVD) and HRV were determined before and after 6 months of monotherapy with indapamide retard 1.5 mg/day. The patients were divided into 2 groups: 30 patients without signs of structural and functional BA remodeling of the (Group 1) and 45 with BA wall hypertrophy and/or endothelial dysfunction.

Results. It was found that the initial HRV indicators characterizing the sympathetic hyperactivity significantly differed in the compared groups. In addition, indapamide retard had a sufficiently high and comparable antihypertensive effect in both groups. In the 2nd group, however, during therapy with Indapamide retard 1.5 mg/day, there was a significant decrease in the intima-media thickness by an average of 12.8% (P=0.013) and, conversely, an increase in EDVD by an average of 25.4% (P<0.001). As a result, specific peripheral vascular resistance decreased by an average of 17.1% (P=0.002). In both groups, patients with left ventricular hypertrophy showed a significant decrease in the left ventricular myocardium mass index: in the 1st group on average by 10.4% (P=0.021) and in the 2nd group by 13.4% (P=0.007). Changes in HRV parameters during therapy with indapamide retard in both groups were statistically insignificant, although they tended to improve the vagosympathetic balance. A direct correlation was found between the standard deviation of the R-R intervals - SDNN and the EDVD index (r=0.34; p=0.007).

Conclusion. It has been shown that the vasoprotective effect of Indapamide retard depends on the severity of vascular remodeling and/or endothelial dysfunction in patients with essential hypertension, both in the presence and absence of sympathetic hyperactivity.