Angiotensin-converting enzyme inhibition in adult hypertensive rats: a stereological study of renal filtration surface area.
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 B2 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 x 10-3 mm3, respectively) compared with controls (glomerular number 25866 +/- 1210 glomeruli/kidney; glomerular volume 2.24 +/- 0.21 x 10-3 mm3). 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 mm2 for SHR, SHR low-dose perindopril, SHR low-dose perindopril + B2 antagonist, SHR high-dose perindopril and SHR high-dose perindopril + B2 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.
Dunstan
H J
HJ
Department of Anatomy and Cell Biology, Monash University, Victoria, Australia.
Briscoe
T A
TA
Bertram
J F
JF
Johnston
C I
CI
Black
M J
MJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000187:drug effects; D009929:Organ Size; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; C094195:S 16118; D001920:Bradykinin; D020913:Perindopril