Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.
We compared the renal vascular responses to angiotensin converting enzyme inhibition and renin inhibition to assess the influence of angiotensin II (Ang II). We examined the renal and endocrine responses to the renin inhibitor enalkiren, to captopril, and to placebo in nine healthy and nine hypertensive men on a 10-mmol sodium diet. Ang II was infused to assess effects of the agents on renal and adrenal responsiveness to Ang II. Plasma Ang II concentration was suppressed similarly with enalkiren and captopril--an identical level of blockade was achieved. Although renal plasma flow was stable during placebo, a substantial rise was seen with both enalkiren (+133 +/- 26 mL/min per 1.73 m2) and captopril (+99.4 +/- 22.6). There was remarkable intrasubject concordance between the renal plasma flow responses to renin inhibition and converting enzyme inhibition (r = .90, P < .004). The vasodilator response to both agents correlated inversely with the fall in renal plasma flow induced by Ang II alone (r = -.66, P < .05). Both agents significantly enhanced the renal vascular response to Ang II (P = .01), and, furthermore, the renal vasodilator response to captopril predicted the potentiation of the renal plasma flow response to Ang II after either agent (enalkiren: r = .91, P < .001; captopril: r = .56, P < .05). Concordance of the maximal renal plasma flow response to the two agents appeared in the hypertensive men as well. Our results indicate that the acute renal response to captopril largely reflects a reduction in Ang II formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fisher
N D
ND
Department of Medicine, Harvard Medical School, Boston, Mass.
Allan
D
D
Kifor
I
I
Gaboury
C L
CL
Williams
G H
GH
Moore
T J
TJ
Hollenberg
N K
NK
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
D000450:Aldosterone; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D004151:Dipeptides; D012083:Renin; D000092502:Renin Inhibitors; C056622:enalkiren