title: Renal and systemic effects of the renin inhibitor remikiren in patients with essential hypertension.
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.
authors.affiliation: Department of Medicine, State University Hospital, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van Paassen
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: P E
authors.initials: PE
authors.lastname: de Jong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D012964:Sodium; D000092502:Renin Inhibitors; C065581:remikiren