Circulation, Vol 85, 1-8, Copyright © 1992 by American Heart Association
W Kiowski, L Linder, C Kleinbloesem, P van Brummelen and FR Buhler
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. METHODS AND 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).
ARTICLES
Blood pressure control by the renin-angiotensin system in normotensive subjects. Assessment by angiotensin converting enzyme and renin inhibition
Division of Cardiology, University Hospital, Basel, Switzerland.
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