Short-term ACE inhibition confers long-term protection against target organ damage.
Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-ω-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n = 36) or tap water (n = 36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (P<0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11 ± 10.0 mm(2) vs. Enal+L: 4 ± 4.4 mm(2)), interstitial fibrosis (Con+L: 3 ± 2.5% vs. Enal+L: 1 ± 1.0%) and tissue macrophages (Con+L: 12 ± 9 mm(2) vs. Enal+L: 5 ± 3.6 mm(2)). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment.
Department of Preclinical Drug Discovery, Faculty of Pharmacy, University of Montreal, Montréal, Québec, Canada.
Taben M
TM
Hale
Susan J
SJ
Robertson
Kevin D
KD
Burns
Denis
D
deBlois
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014508:Urea / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D014508:Urea; D003404:Creatinine; D019331:NG-Nitroarginine Methyl Ester