Abstract-Arterial stiffness, as measured by aortic pulse wave velocity (PWV), is an independent marker of cardiovascular disease and events in both healthy and diseased populations. Although some cardiovascular risk factors, such as age and blood pressure, show a strong association with PWV, the association between heart rate (HR) and PWV is not firmly established. Furthermore, this association has not been investigated at different arterial blood pressures. To study effects of HR on aortic PWV at different mean arterial pressures (MAPs), adult (12 weeks; nϭ7), male, anesthetized Sprague-Dawley rats were randomly paced at HRs of between 300 and 450 bpm, at 50-bpm steps. At each pacing step, aortic PWV was measured across a physiological MAP range of 60 to 150 mmHg by infusing sodium nitroprusside and phenylephrine. When compared at the same MAP, increases in HR resulted in significant increases in PWV at all of the MAPs Ͼ80 mmHg (ANOVA, PϽ0.05), with the greatest significant change of 6.03Ϯ0.93% observed in the range 110 to 130 mmHg. The positive significant association between HR and PWV remained when PWV was adjusted for MAP (ANOVA, PϽ0.001). These results indicate that HR dependency of PWV is different at higher pressures than at lower pressures and that HR may be a confounding factor that should be taken into consideration when performing analysis based on PWV measurements. (Hypertension. 2012;60:528-533.)

Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals (n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.

The effect of angiotensin-converting enzyme inhibition on function and structure of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12-wk-old animals treated with perindopril (3 mg·kg(-1)·day(-1) po) from age 6-12 wk. Tail-cuff systolic pressures were recorded over the treatment period. After PWV measurements, animals were euthanized and the aorta was removed for histomorphological and calcium analysis. Hypertension in LPK at 6 and 12 wk was associated with a shift of the PWV curve upward and to the right, indicating a decrease in aortic compliance, which was significantly reduced by perindopril. LPK demonstrated greater aortic calcification (6 wk: 123 ± 19 vs. 65 ± 7 and 12 wk: 406 ± 6 vs. 67 ± 6 μmol/g, P < 0.001, LPK vs. Lewis, respectively). This was reduced by treatment with perindopril (172 ± 48 μmol/g, 12 wk LPK P < 0.001). Medial cross-sectional area and elastic modulus/wall stress of the aorta were greater in LPK vs. Lewis control animals at 6 and 12 wk of age and showed an age-related increase that was prevented by treatment with perindopril (P < 0.001). Perindopril also ameliorated the degradation of elastin, increase in collagen content, and medial elastocalcinosis seen in 12-wk LPK. Overall, perindopril improved the structural and functional indices of aortic stiffness in the LPK rats, demonstrating a capacity for angiotensin-converting enzyme inhibition to limit vascular remodeling in chronic kidney disease.

Early but not late brief ACEi decreased arterial pressure and isobaric wall stiffness in SHR. This was associated with marked alteration of wall structure and the effects persisted after cessation of early treatment. The structural mechanisms responsible for this change varied segmentally along the aortic trunk.