Renal and Systemic Effects of the Renin Inhibitor Remikiren in Patients with Essential Hypertension

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Abstract
Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. We therefore studied the effects of a single oral administration of remikiren on blood pressure and renal function in 16 patients with essential hypertension on a restricted dietary sodium intake. Remikiren induced a peak fall in mean arterial pressure of 8.5 +/- 0.8%. The glomerular filtration rate (GFR) remained stable, whereas the effective renal-plasma flow rose by 11.3 +/- 1.4%. As a consequence, the filtration fraction and the renal vascular resistance fell by 11.7 +/- 1.2% and 17.6 +/- 1.3%, respectively. These systemic and renal hemodynamic changes were more pronounced in individuals with a higher initial immunoreactive renin. Remikiren induced a significant rise in the fractional excretion of sodium [0.38% (0.24-0.52) to 0.50% (0.31-0.76)] and lithium [28.7% (25.0-32.4) to 33.2% (27-39.4)]. Moreover, remikiren induced a decrease in urinary albumin excretion [497 (268-815) to 252 (114-389) micrograms/h]. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.

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