Le VP, Knutsen RH, Mecham RP, Wagenseil JE. Decreased aortic diameter and compliance precedes blood pressure increases in postnatal development of elastin-insufficient mice. Am J Physiol Heart Circ Physiol 301: H221-H229, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00119.2011.-Increased arterial stiffness and blood pressure are characteristic of humans and adult mice with reduced elastin levels caused by aging or genetic disease. Direct associations have been shown between increased arterial stiffness and hypertension in humans, but it is not known whether changes in mechanical properties or increased blood pressure occur first. Using genetically modified mice with elastin haploinsufficiency (Eln ϩ/Ϫ ), we investigated the temporal relationship between arterial mechanical properties and blood pressure throughout postnatal development. Our results show that some mechanical properties are maintained constant regardless of elastin amounts. The peak diameter compliance for both genotypes occurs near the physiologic pressure at each age, which acts to provide maximum pulse dampening. The stress-strain relationships are similar between genotypes and become nonlinear near the systolic pressure for each age, which serves to limit distension under high pressure. Our results also show that some mechanical properties are affected by reduced elastin levels and that these changes occur before measurable changes in blood pressure. Eln ϩ/Ϫ mice have decreased aortic diameter and compliance in ex vivo tests that are significant by postnatal day 7 and increased blood pressure that is not significant until postnatal day 14. This temporal relationship suggests that targeting large arteries to increase diameter or compliance may be an effective treatment for human hypertension. extracellular matrix; vasculature; vessels THE CONDUCTING ARTERIES IN vertebrates are composed of a specialized extracellular matrix (ECM) that is designed to provide elastic recoil that dampens the pulse pressure in distal arteries and reduces the work of the heart. The major ECM components are elastin and collagen, and the ratio of these proteins primarily determines the passive mechanical behavior of the large elastic arteries. Collagen is 100 -1,000 times stiffer than elastin; hence, vessels become stiffer and their elastic recoil function is compromised as the ratio of elastin to collagen is decreased (5). Arterial wall stiffness, as measured by pulse wave velocity (PWV), is independently associated with hypertension in humans and is increased even at the very early stages of the disease, suggesting that it may be a causative factor and not a resulting symptom of essential hypertension (18).Elastin amounts in humans are decreased through elastic fiber fragmentation in normal aging or through genetic mutations that affect elastin synthesis. Genetic mutations that lead to functional elastin haploinsufficiency have been linked to two inherited diseases, supravalvular aortic stenosis and Williams syndrome (7,19). The cardiovascular phenotypes of...