Hypertension, Vol 23, 439-449, Copyright © 1994 by American Heart Association
DJ Campbell, A Kladis and AM Duncan
We examined the dose-related effects of angiotensin-converting enzyme
inhibitors on circulating and tissue levels of angiotensin and bradykinin
peptides by administering perindopril or lisinopril to rats in drinking
water for 7 days. A reduction in the ratio of plasma angiotensin II (Ang
II) to Ang I was seen for 0.006 mg/kg per day perindopril, with an increase
in plasma renin and Ang I at 0.017 mg/kg per day. Plasma Ang II levels did
not decrease until 1.4 mg/kg per day perindopril, at which dose plasma Ang
I levels reached a plateau of an approximate 25-fold increase. The effects
of perindopril on Ang II and Ang I levels in heart, lung, aorta, and brown
adipose tissue were parallel to those observed for plasma. By contrast,
renal Ang I levels did not increase, and renal Ang II levels decreased by
40% at 0.017 mg/kg per day, the same threshold seen for the increase in
plasma renin. Perindopril increased circulating bradykinin-(1-9) levels
approximately eightfold, with a threshold dose of 0.052 mg/kg per day, and
increased bradykinin-(1-9) levels in kidney, heart, and lung in parallel
with the changes observed for plasma. By contrast, aortic and brown adipose
tissue bradykinin-(1-9) and bradykinin-(1-7) levels increased severalfold
for perindopril doses as low as 0.006 mg/kg per day. Lisinopril also
increased aortic bradykinin-(1-9) and bradykinin- (1-7) levels at doses
below the threshold for the decrease in the ratio of Ang II to Ang I. These
data indicate that renal Ang II levels and vascular bradykinin-(1-9) levels
respond to low doses of converting enzyme inhibitor and may be important
mediators of the effects of these compounds. The parallel increases in
bradykinin-(1-9) and bradykinin-(1- 7) levels in aorta and brown adipose
tissue, at inhibitor doses below the threshold for inhibition of Ang I
conversion, may result from a mechanism different from inhibition of
"classic" angiotensin-converting enzyme.
ARTICLES
Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
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C. M. Ferrario, M. C. Chappell, E. A. Tallant, K. B. Brosnihan, and D. I. Diz Counterregulatory Actions of Angiotensin-(1-7) Hypertension, September 1, 1997; 30(3): 535 - 541. [Abstract] [Full Text]
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C. V. Lima, R. D. Paula, F. L. Resende, M. C. Khosla, and R. A. S. Santos Potentiation of the Hypotensive Effect of Bradykinin by Short-term Infusion of Angiotensin-(1-7) in Normotensive and Hypertensive Rats Hypertension, September 1, 1997; 30(3): 542 - 548. [Abstract] [Full Text]
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R. R. Britto, R. A. S. Santos, C. R. Fagundes-Moura, M. C. Khosla, and M. J. Campagnole-Santos Role of Angiotensin-(1-7) in the Modulation of the Baroreflex in Renovascular Hypertensive Rats Hypertension, September 1, 1997; 30(3): 549 - 556. [Abstract] [Full Text]
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A. Abbas, G. Gorelik, L. A. Carbini, and A. G. Scicli Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats Hypertension, August 1, 1997; 30(2): 217 - 221. [Abstract] [Full Text]
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K. C. Wollert, R. Studer, K. Doerfer, E. Schieffer, C. Holubarsch, H. Just, and H. Drexler Differential Effects of Kinins on Cardiomyocyte Hypertrophy and Interstitial Collagen Matrix in the Surviving Myocardium After Myocardial Infarction in the Rat Circulation, April 1, 1997; 95(7): 1910 - 1917. [Abstract] [Full Text]
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K. F. Hilgers, V. Reddi, J. H. Krege, O. Smithies, and R. A. Gomez Aberrant Renal Vascular Morphology and Renin Expression in Mutant Mice Lacking Angiotensin-Converting Enzyme Hypertension, January 1, 1997; 29(1): 216 - 221. [Abstract] [Full Text] [PDF]
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P. Li, M. C. Chappell, C. M. Ferrario, and K. B. Brosnihan Angiotensin-(1-7) Augments Bradykinin-Induced Vasodilation by Competing With ACE and Releasing Nitric Oxide Hypertension, January 1, 1997; 29(1): 394 - 398. [Abstract] [Full Text] [PDF]
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S. B. Harrap and J. B. O'Sullivan Cardiac Transplantation, Perindopril, and Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats Hypertension, October 1, 1996; 28(4): 622 - 626. [Abstract] [Full Text]
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K. B. Brosnihan, P. Li, and C. M. Ferrario Angiotensin-(1-7) Dilates Canine Coronary Arteries Through Kinins and Nitric Oxide Hypertension, March 1, 1996; 27(3): 523 - 528. [Abstract] [Full Text]
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A. F. Dominiczak, A. M. Devlin, W. K. Lee, N. H. Anderson, D. F. Bohr, and J. L. Reid Vascular Smooth Muscle Polyploidy and Cardiac Hypertrophy in Genetic Hypertension Hypertension, March 1, 1996; 27(3): 752 - 759. [Abstract] [Full Text]
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W. R. Fitzgibbon, A. A. Jaffa, R. K. Mayfield, and D. W. Ploth Role of Kinins in the Renal Response to Enalaprilat in Normotensive and Hypertensive Rats Hypertension, February 1, 1996; 27(2): 235 - 244. [Abstract] [Full Text]
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R. D. Paula, C. V. Lima, M. C. Khosla, and R. A.S. Santos Angiotensin-(1-7) Potentiates the Hypotensive Effect of Bradykinin in Conscious Rats Hypertension, December 1, 1995; 26(6): 1154 - 1159. [Abstract] [Full Text]
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D. J. Campbell, A.-M. Duncan, A. Kladis, and S. B. Harrap Angiotensin Peptides in Spontaneously Hypertensive and Normotensive Donryu Rats Hypertension, May 1, 1995; 25(5): 928 - 934. [Abstract] [Full Text]
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D. J. Campbell, P. Rong, A. Kladis, B. Rees, D. Ganten, and S. L. Skinner Angiotensin and Bradykinin Peptides in the TGR(mRen-2)27 Rat Hypertension, May 1, 1995; 25(5): 1014 - 1020. [Abstract] [Full Text]
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H. Nakamoto, C. M. Ferrario, S. B. Fuller, D. L. Robaczewski, E. Winicov, and R. H. Dean Angiotensin-(1-7) and Nitric Oxide Interaction in Renovascular Hypertension Hypertension, April 1, 1995; 25(4): 796 - 802. [Abstract] [Full Text]
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M. G. Melaragno and G. D. Fink Enhanced Slow Pressor Effect of Angiotensin II in Two-Kidney, One Clip Rats Hypertension, February 1, 1995; 25(2): 288 - 293. [Abstract] [Full Text]
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W. Huang, Y. Gallois, N. Bouby, P. Bruneval, D. Heudes, M.-F. Belair, J. H. Krege, P. Meneton, M. Marre, O. Smithies, et al. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse PNAS, November 6, 2001; 98(23): 13330 - 13334. [Abstract] [Full Text] [PDF]
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A. E. Loot, A. J.M. Roks, R. H. Henning, R. A. Tio, A. J.H. Suurmeijer, F. Boomsma, and W. H. van Gilst Angiotensin-(1-7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats Circulation, April 2, 2002; 105(13): 1548 - 1550. [Abstract] [Full Text] [PDF]
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