title: Blood pressure control by the renin-angiotensin system in normotensive subjects. Assessment by angiotensin converting enzyme and renin inhibition.
abstract: BACKGROUND
  The participation of the renin-angiotensin system in the control of blood pressure in normal, sodium-replete subjects is not clear. The use of a specific inhibitor of human renin should allow a better delineation of the importance of this system.
  
  
  RESULTS
  Blood pressure responses were measured 1 hour after randomized, double-blind administration of the renin inhibitor Ro 42-5892 (600 mg p.o.) or the angiotensin converting enzyme inhibitor captopril (50 mg p.o.) in 20 healthy men on an ad libitum sodium diet. Effective inhibition of the renin-angiotensin system by either compound was indicated by increases of immunoreactive renin associated with an increase of angiotensin I production rate of 67.8 +/- 33.6% after captopril and a decrease of 79.5 +/- 16.4% after Ro 42-5892. Furthermore, Ro 42-5892 decreased plasma renin activity by 64%. Whereas intra-arterial diastolic (60 +/- 5.1 to 51.4 +/- 7.2 mm Hg, p less than 0.01) and mean arterial (77.7 +/- 6.0 to 71.4 +/- 8.5 mm Hg, p less than 0.001) pressures decreased after captopril, they remained unchanged after Ro 42-5892. Captopril, but not Ro 42-5892, increased forearm blood flow (2.4 +/- 0.8 versus 1.9 +/- 0.8 ml/min/100 ml, p less than 0.01) and significantly enhanced the increase of forearm blood flow to brachial artery infusions of bradykinin (0.15, 1.5, 5, 15, and 50 ng/min/100 ml; 5 minutes each) from 744 +/- 632% to 1,383 +/- 514% (p less than 0.01). Furthermore, repeat bradykinin infusions resulted in further decreases of blood pressure (from mean pressure of 71.4 +/- 8.5 to 63.2 +/- 7.6 mm Hg, p less than 0.01) only after captopril. Changes of blood pressure after captopril were unrelated to baseline plasma renin activity but correlated with captopril-induced enhancement of vasodilation to bradykinin (r = 0.68, p less than 0.05).
  
  
  CONCLUSIONS
  The lack of blood pressure effects of renin inhibition in contrast to angiotensin converting enzyme inhibition suggests that the renin-angiotensin system does not contribute significantly to blood pressure control in normotensive, sodium-replete subjects. The hypotensive activity of angiotensin converting enzyme inhibitors may result from additional hormonal effects, for example, inhibition of bradykinin degradation and/or subsequent increases of vasodilating prostaglandins or endothelium-derived relaxing factor(s).
authors.affiliation: Division of Cardiology, University Hospital, Basel, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Kiowski
authors.forename: L
authors.initials: L
authors.lastname: Linder
authors.forename: C
authors.initials: C
authors.lastname: Kleinbloesem
authors.forename: P
authors.initials: P
authors.lastname: van Brummelen
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles; D008297:Male; D012016:Reference Values; D012083:Renin / Q000097:blood / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000502:physiology*; D000092502:Renin Inhibitors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin; D002216:Captopril; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C065581:remikiren