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Angiotensin‐converting enzyme inhibition in adult hypertensive rats: A stereological study of renal filtration surface area
Author(s) -
Dunstan HJ,
Briscoe TA,
Bertram JF,
Johnston CI,
Black MJ
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03793.x
Subject(s) - perindopril , renal function , endocrinology , medicine , angiotensin converting enzyme , kidney , ace inhibitor , filtration fraction , bradykinin , blood pressure , renal blood flow , renal circulation , urology , receptor
Summary 1. Angiotensin‐converting enzyme (ACE) inhibitor treatment leads to beneficial effects on kidney function. The aim of the present study was to determine whether ACE inhibition at high or low doses affects glomerular capillary surface area and length, glomerular number or total renal filtration surface area in rats with established hypertension and, if so, to determine whether these effects are mediated through bradykinin potentiation. 2. Spontaneously hypertensive rats (SHR) were treated with the ACE inhibitor perindopril at either 3 or 0.1 mg/kg per day (high and low doses, respectively) from 16 to 24 weeks of age. Some rats were concomitantly treated with the bradykinin B 2 receptor antagonist S16118 (10 nmol/kg per day). Blood pressure was measured twice weekly during the treatment period. At 24 weeks of age, rats were perfusion fixed at 140 mmHg, the kidneys removed, embedded in resin and examined stereologically to estimate glomerular number and volume, length and surface area of glomerular capillaries and total renal filtration surface area. 3. High‐ and low‐perindopril treatment significantly reduced systolic blood pressure compared with control SHR. However, the rats treated with low‐dose perindopril were still considered hypertensive. Neither low‐dose nor high‐dose perindopril treatment had any observable effect on glomerular number (23 876 ± 1201 vs 26 240 ± 1465 glomeruli/kidney, respectively) or volume (2.25 ± 0.21 and 1.96 ± 0.06 × 10 −3 mm 3 , respectively) compared with controls (glomerular number 25 866 ± 1210 glomeruli/kidney; glomerular volume 2.24 ± 0.21 × 10 −3 mm 3 ). As a result, there was no significant difference in total renal filtration surface area between any of the experimental groups (8161.6 ± 550.9, 8699.7 ± 427.6, 9081.9 ± 453.6, 8830.2 ± 521.2 and 8559.4 ± 341.4 mm 2 for SHR, SHR low‐dose perindopril, SHR low‐dose perindopril + B 2 antagonist, SHR high‐dose perindopril and SHR high‐dose perindopril + B 2 antagonist, respectively). Coadministration of the bradykinin antagonist had no observable effect on any of the parameters studied. 4. In conclusion, because neither high‐dose nor low‐dose perindopril had any effect on total renal filtration surface area, the observed beneficial effects of ACE inhibition on kidney function are not the result of enhancement in glomerular capillary surface area.