Nephroprotection by long-term ACE inhibition with ramipril in spontaneously hypertensive stroke prone rats.
BACKGROUND
The effect of life-long treatment with the ACE inhibitor ramipril on hypertension-induced histological changes in the kidney was tested in stroke-prone spontaneously hypertensive rats (SHR-SP).


METHODS
One-month-old pre-hypertensive SHR-SP were randomized into three groups of 45 animals each, and exposed via drinking water for their lifetime to a dose of: 1 mg.kg-1.d-1 ramipril (antihypertensive dose, HRA); 10 micrograms.kg-1.d-1 slight dose of ramipril (non-antihypertensive dose, LRA); or placebo. Histological and biochemical assessments were conducted after 15 months in ten rats each, when about 80% of the placebo group had died.


RESULTS
Kidneys from placebo treated SHR-SP showed pronounced arterial wall hypertrophy and sclerosis, arterial fibrinoid necrosis, glomerulopathy and tubular interstitial injury that were, in concert with normalized blood pressure, completely prevented by HRA treatment. LRA treatment did not affect any blood pressure increase, and also attenuated the development of arterial wall hypertrophy, sclerosis and arterial fibrinoid necrosis, though to a minor extent only, but did not change glomerular and tubulointerstitial degeneration. These effects of ramipril were associated with a dose-dependent inhibition of plasma and renal tissue ACE activities as well as lower serum concentrations of creatinine, but there were no changes in serum potassium.


CONCLUSIONS
Life-long HRA-induced ACE inhibition protects against hypertension-induced renal damages in SHR-SP. This is associated with a doubling of the lifespan in these animals.
Linz
W
W
DG Cardiovascular Research, Hoechst Marion Roussel, Frankfurt am Main, Germany. wolfgang.linzhmrag.com
Becker
R H
RH
Schölkens
B A
BA
Wiemer
G
G
Keil
M
M
Langer
K H
KH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006974:Hypertension, Malignant / Q000097:blood / Q000235:genetics / Q000473:pathology; D006984:Hypertrophy / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics / Q000502:physiology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril