Biomechanics models predict increasing smooth muscle tone as a novel therapeutic target for central arterial dysfunction in hypertension

INTRODUCTION: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations. METHODS: Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis. RESULTS: A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm 2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm 2 . CONCLUSION: In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.