Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy.
Aging is associated with cardiac hypertrophy and arterial stiffening possibly associated with accumulation of advanced glycation end products (AGEs). We evaluated the effect of aminoguanidine, an inhibitor of AGE production, on end-stage alterations of renal and cardiovascular systems. Normotensive WAG/Rij rats were treated from 24 to 30 mo with aminoguanidine and compared with a control group. Aminoguanidine did not modify body and kidney weights but prevented the age-related cardiac hypertrophy (heart weight: 1276 +/- 28 mg and 1896 +/- 87 mg in 24- and 30-mo-old control animals and 1267 +/- 60 mg in 30-mo-old treated rats, P < 0.01). The increase in mesangial surface in aging rats was reduced by 30% by aminoguanidine. Collagen content of the arterial wall increased between 24 and 30 mo whereas elastin content, media thickness, and smooth muscle cell number remained unchanged. Aminoguanidine did not affect these parameters; however, the age-related increase in aortic impedance (12.4 +/- 1.4 and 18.2 +/- 1.9 10(3).dyne.sec.cm-5 in control 24- and 30-mo-old rats, P < 0.01) and the decrease in carotid distensibility (0.79 +/- 0.11 and 0.34 +/- 0. 07 mm Hg-1 in control 24- and 30-mo-old rats, P < 0.01) were prevented by aminoguanidine. The prevention of arterial stiffening and cardiac hypertrophy in the absence of changes in collagen and elastin content suggests that the effect of aminoguanidine is related to a decrease in the AGE-induced cross-linking of the extracellular matrix.
Corman
B
B
Service de Biologie Cellulaire, Commissariat à l'Energie Atomique, Centre d'Etudes de Saclay, Gif sur Yvette, 91191 Cedex, France.
Duriez
M
M
Poitevin
P
P
Heudes
D
D
Bruneval
P
P
Tedgui
A
A
Levy
B I
BI
D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004548:Elasticity / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D051381:Rats
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine