Background-Arterial stiffness is an independent determinant of cardiovascular risk, and arterial stiffening is the predominant abnormality in systolic hypertension. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9) and MMP-2. We hypothesized that elastase activity would be related to arterial stiffness and tested this using isolated systolic hypertension (ISH) as a model of stiffening and separately in a large cohort of healthy individuals. Methods and Results-A total of 116 subjects with ISH and 114 matched controls, as well as 447 individuals free from cardiovascular disease were studied. Aortic and brachial pulse wave velocity (PWV) and augmentation index were determined. Blood pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured. Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH subjects compared with controls (Pϭ0.001). MMP-9 levels correlated linearly and significantly with aortic (rϭ0.45; Pϭ0.001) and brachial PWV (rϭ0.22; Pϭ0.002), even after adjustments for confounding variables. In the younger, healthy subjects, MMP-9 and SEA were also independently associated with aortic PWV. Conclusions-Aortic stiffness is related to MMP-9 levels and SEA, not only in ISH, but also in younger, apparently healthy individuals. This suggests that elastases including MMP-9 may be involved in the process of arterial stiffening and development of ISH.

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Abstract-NO modulates resting blood pressure and wave reflection. The effect of NO on exercise central hemodynamics is unknown but has important implications relating to cardiovascular risk. The aim of this study was to determine the contribution of NO to pulse pressure (PP) amplification and wave reflection during exercise. Twelve healthy men aged 29Ϯ1 years (meanϮSEM) undertook cycle exercise at 60% of their maximal heart rate. Noninvasive measures of central blood pressure, estimated aortic pulse wave velocity, and wave reflection (augmentation index) were obtained by pulse wave analysis during intravenous infusion of saline (control), N G -monomethyl-L-arginine (a NO-synthase inhibitor), or noradrenaline (control vasoconstrictor). PP amplification was defined as the ratio of peripheral to central PP. Cardiac output and stroke volume were determined by electric bioimpedance. Both N G -monomethyl-L-arginine and noradrenaline caused a significant increase in mean arterial pressure (PϽ0.01) and augmentation index (PϽ0.01), as well as reduced ratio of peripheral to central PP (PϽ0.05) at baseline. Exercise caused a significant increase in the ratio of peripheral to central PP (PϽ0.001), whereas augmentation index and estimated aortic pulse wave velocity declined (for both PϽ0.05) during all 3 of the infusion protocols. However, no significant differences were observed in augmentation index, ratio of peripheral to central PP, or estimated aortic pulse wave velocity between infusion procedures (PϾ0.50) during exercise. Also, heart rate, peripheral vascular resistance, and cardiac output did not differ during exercise between saline, N G -monomethyl-L-arginine, or noradrenaline. Although we cannot rule out other vasodilator mechanisms having adjusted for NO blockade, our results indicate that NO does not solely contribute to systemic arterial stiffness or altered blood pressure amplification during light exercise.