Uncontrolled Arterial Hypertension: Kidney, Neurohormonal Imbalance, and Approaches to Antihypertensive Drug Therapy

Resistant and refractory arterial hypertensions are two distinct clinical phenotypes of uncontrolled arterial hypertension (AH), which differ in their sensitivity to antihypertensive drug therapy. The review presents data obtained in clinical studies devoted to elucidating the involvement of disorders of neurohormonal status and renal function in the formation of resistant and refractory arterial hypertension, to and the development of new approaches to increasing the effectiveness of antihypertensive therapy in these patient's populations. The results of these studies have shown that in patients with uncontrolled arterial hypertension, despite prolonged intake ≥ 3 antihypertensive drugs with different mechanisms of action, including a diuretic, excess sodium reabsorption persists in the distal segments of nephron due to increased aldosterone activity and sympathetic nervous system hyperactivity. In this regard, special attention has been paid to the data of PATHWAY-2, PATHWAY-3 and ReHOT trials that in patients with resistant AH tested the clinical efficacy of spironolactone, amiloride, and antiadrenergic drugs bisoprolol, doxazosin and clonidine, suppressing activity of the sympathetic nervous system.