doi: 10.1161/hy1001.096211
(Hypertension. 2001;38:943.)
© 2001 American Heart Association, Inc.
Fourth Workshop on Structure and Function of Large Arteries |
Aminoguanidine and Aortic Wall Mechanics, Structure, and Composition in Aged Rats
From the Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Université Henri Poincaré-Nancy 1 (C.C., P.K., P.L., J.A., I. L.-I.), Nancy, France; and Service de Biologie Cellulaire, C.E.A./Saclay (B.C.), Gif sur Yvette, France.
Correspondence to Dr Jeffrey Atkinson, Laboratoire de Pharmacologie Cardiovasculaire, EA 3116, Faculté de Pharmacie, Université Henri Poincaré-Nancy 1, 5 rue Albert Lebrun, 54000 Nancy, France. E-mail atkinson{at}pharma.u-nancy.fr
Abstract
Abstract—— With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.
Key Words: age • collagen • rats, inbred strains • aorta
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