Abstract
Background: Physiologically, the aorta is less stiff than peripheral conductive arteries, creating an arterial stiffness gradient, protecting microcirculation from high pulsatile pressure. However, the pharmacological manipulation of arterial stiffness gradient has not been thoroughly investigated. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio).Methods: In 93 subjects (age: 61 years, men: 67%, chronic kidney disease [CKD]: 41%), aortic, brachial, and femoral stiffnesses were determined by cf-PWV, carotid-radial (cr-PWV), and femoral-dorsalis pedis artery (fp-PWV) PWVs, respectively. The measurements were repeated 5 min after the sublingual administration of NTG (0.4 mg). The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fp-PWV, respectively. The central pulse wave profile was determined by radial artery tonometry through the generalized transfer function.Results: At baseline, cf-PWV, cr-PWV, and fp-PWV were 12.12 ± 3.36, 9.51 ± 1.81, and 9.71 ± 1.89 m/s, respectively. After the administration of NTG, there was a significant reduction in cr-PWV of 0.86 ± 1.27 m/s (p < 0.001) and fp-PWV of 1.12 ± 1.74 m/s (p < 0.001), without any significant changes in cf-PWV (p = 0.928), leading to a significant increase in the AB-PWV ratio (1.30 ± 0.39 vs. 1.42 ± 0.46; p = 0.001) and AF-PWV ratio (1.38 ± 0.47 vs. 1.56 ± 0.53; p = 0.001). There was a significant correlation between changes in the AF-PWV ratio and changes in the timing of wave reflection (r = 0.289; p = 0.042) and the amplitude of the heart rate-adjusted augmented pressure (r = − 0.467; p < 0.001).Conclusion: This study shows that acute administration of NTG reduces PWV of muscular arteries (brachial and femoral) without modifying aortic PWV. This results in an unfavorable profile of AB-PWV and AF-PWV ratios, which could lead to higher pulse pressure transmission into the microcirculation.
Highlights
Aortic stiffness, determined by aortic pulse wave velocity (PWV), is a hallmark of vascular aging and an independent cardiovascular risk factor in various clinical conditions ranging from hypertension to end-stage kidney disease (Blacher et al, 1999a,b; Laurent et al, 2001; Cruickshank et al, 2002; Karras et al, 2012)
In chronic kidney disease (CKD) patients, we have shown that the changes in arterial stiffness gradient are guided by an increase in aortic stiffness and by a decrease in the stiffness of the medium-sized muscular arteries such as the brachial artery (Utescu et al, 2013; Fortier et al, 2015)
This study shows that acute administration of NTG reduces brachial and femoral PWVs without affecting aortic PWV, causing an increase in the AB-PWV and AF-PWV ratios
Summary
Aortic stiffness, determined by aortic pulse wave velocity (PWV), is a hallmark of vascular aging and an independent cardiovascular risk factor in various clinical conditions ranging from hypertension to end-stage kidney disease (Blacher et al, 1999a,b; Laurent et al, 2001; Cruickshank et al, 2002; Karras et al, 2012). Due to the heterogeneity of vascular wall composition and diameter, there is an increase in arterial stiffness (stiffness gradient) from the heart to the periphery. This gradient in arterial stiffness results in a gradual attenuation of forward pressure wave along the arterial tree down to the microcirculation, where the pulsatility must be minimal. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio)
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