Renin inhibition: a tool to assess the role of the renin-angiotensin aldosterone system in renal hemodynamics and sodium handling in human hypertension

Abstract

Section I of this thesis- Pharmacology- focuses on the systemic and renal effects of the specific renin inhibitor remikiren (Ro 42-5892) in hypertensive patients with different degrees of renal function impairment. It tests the hypothesis that remikiren is an effective antihypertensive agent with a favorable renal profile. This was the first study on the renal effects of an orally administered renin inhibitor in this target population. In section II- Pathophysiology- the renin inhibitor is used as a specific pharmacologic tool to study the role of the RAAS in the pathophysiology of renal sodium handling in primary hypertension. Since it is not feasible to measure local intrarenal RAAS-activity, the response to remikiren was used as a surrogate indicator for the state of activation of the RAAS. In these studies we tested the hypothesis that dysregulation of the (intrarenal) RAAS, leading to inappropriately elevated levels of the effector hormone angiotensin II, plays al role in the impaired renal sodium handling and abnormal renal hemodynaics, either or not in mutual interaction, in primary hypertension. ... Zie: Summary.