Hypertension, Vol 18, 763-773, Copyright © 1991 by American Heart Association
DJ Campbell, AC Lawrence, A Towrie, A Kladis and AJ Valentijn
We compared the effects of the converting enzyme inhibitor perindopril on
components of the renin-angiotensin system in plasma and kidney of male
Sprague-Dawley rats administered perindopril in their drinking water at two
doses (1.4 and 4.2 mg/kg) over 7 days. Eight angiotensin peptides were
measured in plasma and kidney: angiotensin-(1-7), angiotensin II,
angiotensin-(1-9), angiotensin I, angiotensin-(2-7), angiotensin III,
angiotensin-(2-9), and angiotensin-(2-10). In addition, angiotensin
converting enzyme activity, renin, and angiotensinogen were measured in
plasma, and renin, angiotensinogen, and their respective messenger RNAs
were measured in kidney; angiotensinogen messenger RNA was also measured in
liver. In plasma, the highest dose of perindopril reduced angiotensin
converting enzyme activity to 11% of control, increased renin 200-fold,
reduced angiotensinogen to 11% of control, increased angiotensin-(1-7),
angiotensin I, angiotensin-(2-7), and angiotensin-(2-10) levels 25-, 9- ,
10-, and 13-fold, respectively; angiotensin II levels were not
significantly different from control. By contrast, for the kidney,
angiotensin-(1-7), angiotensin I, angiotensin-(2-7), and angiotensin-(2-
10) levels did not increase; angiotensin II levels fell to 14% of control,
and angiotensinogen fell to 12% of control. Kidney renin messenger RNA
levels increased 12-fold, but renal renin content and angiotensinogen
messenger RNA levels in kidney and liver were not influenced by perindopril
treatment. These results demonstrate a differential regulation of
angiotensin peptides in plasma and kidney and provide direct support for
the proposal that the cardiovascular effects of converting enzyme
inhibitors depend on modulation of tissue angiotensin systems. Moreover,
the failure of kidney angiotensin I levels to increase with perindopril
treatment, taken together with the fall in kidney angiotensinogen levels,
suggests that angiotensinogen may be a major rate-limiting determinant of
angiotensin peptide levels in the kidney.
ARTICLES
Differential regulation of angiotensin peptide levels in plasma and kidney of the rat
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
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