(Hypertension. 1995;25:674-678.)
© 1995 American Heart Association, Inc.
Articles |
Expression of Angiotensin-Converting Enzyme in Renovascular Hypertensive Rat Kidney
From the Nephrology Laboratory, Department of Medicine IV, University of Erlangen, and Max-Delbrück Center, Berlin-Buch (J.W.), Germany.
Correspondence to Karl F. Hilgers, MD, Child Health Research Center, MR4 Building Room 2001, University of Virginia, Park Place Ln 300, Charlottesville, VA 22908.
Abstract We hypothesized that the gene expression of angiotensinogen, angiotensin-converting enzyme, and angiotensin II type 1 receptor, in addition to renin, is increased in kidneys after renal artery stenosis. Two-kidney, one clip renovascular hypertension was initiated in Sprague-Dawley rats by clipping of the left renal artery; control rats were sham operated. Blood pressure was not changed for the first 2 days after clipping but was elevated on day 4 (mean arterial pressure, 104±4 versus 87±2 mm Hg in sham-operated control rats, P<.002) and increased further during the next 24 days. Rats were killed 2, 4, 7, 14, and 28 days after clipping or sham operation, and poly(A)+-purified renal cortical RNA was analyzed by Northern blotting. Autoradiographs were quantitated by densitometry and normalized for the expression of a housekeeping gene. Renin expression was increased in the clipped kidney (by 149% on day 2) and decreased in the nonclipped kidney (by 82% on day 2), compared with kidneys of control rats. Expression of the angiotensin-converting enzyme was increased in clipped kidneys from the first day after clipping (158%) and throughout the experiment (66% on day 28), but was unchanged or slightly decreased in nonclipped kidneys. Angiotensinogen mRNA showed little change. Angiotensin II type 1 receptor expression was decreased in nonclipped kidneys but unchanged during the first 7 days in clipped kidneys. Our results show that components of the renin-angiotensin system other than renin are also differentially expressed in clipped kidneys. Increased expression of the angiotensin-converting enzyme in poststenotic kidneys occurs very early in the development of renovascular hypertension and may contribute to increased intrarenal angiotensin II formation.
Key Words: hypertension, renovascular • kininase II • receptors, angiotensin • RNA, messenger
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