Key result
Restoring normal BP in hypertensive mice only partially reverses aortic stiffness.
Why the study?
Hypertension drives vascular remodeling and stiffening, but whether restoring normal BP fully restores vascular stiffness toward normotensive controls remained unestablished.
Does restoring normal blood pressure fully reverse vascular stiffness toward that of normotensive controls in hypertensive mice?
Does restoring normal blood pressure fully reverse vascular stiffness toward that of normotensive controls in hypertensive mice?
Restoring normal blood pressure in hypertensive mice reverses passive matrix stiffness but fails to fully reverse in vivo vascular stiffness due to persistent endothelial and vascular smooth muscle cell dysfunction.
May not fully reverse aortic stiffness with BP normalization in hypertension; leaves open persistent vascular cell dysfunction as a target in animal models.
Background: Hypertension is a well-established driver of vascular remodeling and stiffening. The goal of this study was to evaluate whether restoring normal blood pressure (BP) fully restores vascular stiffness toward that of normotensive controls. Methods: C57Bl6/J male mice received angiotensin II (angII; 1 µg/kg/min) via infusion pump for 8 weeks (hypertension group: HH), angII for 4 weeks (hypertension group: H4), angII for 4 weeks followed by 4 weeks of recovery (reversal group: HN), or sham treatment (normotensive group: NN). BP, heart rate, and pulse wave velocity (PWV) were measured longitudinally. At the end of the study period, aortas were harvested for testing of vasoreactivity, passive mechanical properties, and vessel structure. Results: The HH group exhibited a sustained increase in BP and PWV over the 8-week period (p<0.01). In the HN group, BP and PWV increased during the 4-week angII infusion, and, though BP was restored during the 4-week recovery, PWV exhibited only partial restoration (p<0.05). Heart rate was similar in all cohorts. Compared to NN controls, both HH and HN groups had significantly increased wall thickness (p<0.05 HH vs. NN, p<0.01 HN vs. NN ), mucosal extracellular matrix accumulation (p<0.0001 HH vs. NN, p<0.05 HN vs. NN), and intralamellar distance (p<0.001 HH vs. NN, p<0.01 HN vs. NN). Both intact and decellularized vessels were noted to have significantly higher passive stiffness in the HH and H4 cohorts than in NN controls (p<0.0001). However, in the HN cohort, intact vessels were only modestly stiffer than those of NN controls, and decellularized HN vessels were identical to those from the NN controls. Compared to NN controls, the HH and HN cohorts exhibited significantly diminished phenylephrine-induced contraction (p<0.000) and endothelium-dependent vasodilation (p<0.05). Conclusion: Hypertension causes a significant increase in in vivo aortic stiffness that is only partially reversible after BP normalization. Although hypertension does lead to matrix stiffening, restoration of BP restores matrix mechanics to levels similar to those of normotensive controls. Nevertheless, endothelial and vascular smooth muscle cell dysfunction persist after restoration of normotension. This dysfunction is, in part, responsible for augmented PWV after restoration of BP.
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Steppan et al. (2020) studied Hypertension (n=40). Angiotensin II infusion followed by recovery vs. Sham treatment (normotensive) and continuous Angiotensin II was evaluated on Pulse wave velocity (PWV) as an index of in vivo vascular stiffness (p=<0.05). Restoring normal blood pressure in hypertensive mice after 4 weeks of angiotensin II infusion only partially reversed in vivo aortic stiffness (pulse wave velocity) compared to normotensive controls (p < 0.05).
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