Carotid artery hemodynamics: observing patient-specific changes with amlodipine and lisinopril by using MR imaging computation fluid dynamics.

PURPOSE: To assess whether using magnetic resonance (MR) imaging combined with computational fluid dynamics (CFD) could reveal changes in common carotid artery (CCA) flow and wall shear stress (WSS) that might contribute to differences in CCA remodeling between amlodipine, a calcium channel blocker, and lisinopril, an angiotensin-converting enzyme inhibitor, despite similar reductions in blood pressure (BP). MATERIALS AND METHODS: Institutional review board approval was obtained, and participants gave informed consent. Nine subjects with hypertension were recruited into a double-blind placebo-controlled randomized three-way crossover study to compare the hemodynamic effects of 7 days of treatment with placebo, amlodipine, or lisinopril. After each treatment period, patients underwent CCA ultrasonography, BP measurement, and MR imaging with CFD. Analyses were performed by using repeated-measures analysis of variance, followed by the Tukey test or the Wilcoxon matched-pairs test. RESULTS: Amlodipine and lisinopril lowered BP similarly, but CCA flow rate was significantly higher (P < .01) and distal vascular resistance was lower (P = .016) after amlodipine treatment than after lisinopril treatment. WSS on the inner wall of the CCA was significantly lower after lisinopril treatment than after amlodipine treatment (P = .03). The change in WSS in the CCA correlated with the change in vascular resistance (r = -0.85, P < .001). CONCLUSION: Amlodipine causes increased blood flow and increased time-averaged WSS in the CCA compared with lisinopril, despite similar reductions in BP. Differences in the subacute hemodynamic effects of amlodipine and lisinopril could contribute to the differences in CCA remodeling seen in long-term studies. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100788/-/DC1.

Impaired recovery of intracellular calcium and force after activation in isolated myometrial and subcutaneous resistance arteries from women with preeclampsia.

OBJECTIVES: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, but its cause is poorly understood. This study investigated whether there is an abnormality of intracellular calcium ([Ca2=]i) and tension during recovery from activation in isolated resistance arteries in preeclampsia and investigated the underlying mechanisms. METHODS: Subcutaneous and myometrial resistance arteries from preeclamptic, normotensive pregnant and nonpregnant women were mounted on an isometric myograph and loaded with fura-2 to allow simultaneous measurement of force and [Ca2+]i. Arteries were activated by a high-potassium solution or noradrenaline, and the rate of decline in force and [Ca2+]i examined following washout. RESULTS: Basal tone and [Ca2+]i and rise in force and [Ca2+]i induced by high-potassium solution did not differ between groups but the rate of decline after washout was significantly slowed in both subcutaneous and myometrial arteries from preeclamptic women as compared with normotensive pregnant or nonpregnant women. The rate of decline in force after noradrenaline was also slowed in arteries from preeclamptic women. In subcutaneous resistance arteries from nonpregnant women, removal of the endothelium did not affect the rate of decline in force after high-potassium solution. However, inhibition of the plasma membrane Ca ATPase with carboxyeosin mimicked the findings seen in preeclampsia. In contrast, inhibition of the sarcoplasmic endoreticulum Ca ATPase with cyclopiazonic acid had no effect on the rate of decline in force or [Ca2+]i. CONCLUSION: The rate of relaxation and decline in [Ca2+]i in resistance arteries are impaired in preeclampsia. This may be mediated by decreased activity of plasma membrane Ca2+ ATPase and could be a mechanism contributing to elevated peripheral resistance and raised blood pressure in preeclampsia.

Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study.

BACKGROUND: Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol+/-thiazide-based versus amlodipine+/-perindopril-based therapy) on derived central aortic pressures and hemodynamics. METHODS AND RESULTS: The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Delta0.7 mm Hg; 95% CI, -0.4 to 1.7; P=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Delta4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, Delta3.0 mm Hg; 95% CI, 2.1 to 3.9; P<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc-defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P<0.0001; adjusted for baseline variables, P<0.05). CONCLUSIONS: BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.