Abstract
Arterial stiffness may contribute to the pathogenesis of hypertension. The goal of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic stiffening-induced hypertension through ETA receptor activation. An increase in aortic stiffness was created by use of a non-constrictive restraint, NCR on the abdominal aortic surface. A group of rats underwent aortic NCR or sham operation for 12 weeks and were then treated with ETA receptor antagonist BQ-123 for 3 weeks. We found that 12 weeks of aortic NCR significantly increased pulse and mean pressure and altered peripheral flow pattern, accompanied by an increased serum ET-1 level (p < 0.05). The increase in aortic stiffness (evidenced by an elevated pulse wave velocity) caused hypertrophic structural remodeling and decreased arterial compliance, along with an impaired endothelial function in peripheral small arteries. BQ-123 treatment only partially attenuated peripheral arterial hypertrophy and restored arterial compliance, but completely recovered endothelium function, and consequently restored local flow and lowered blood pressure. Our findings underscore the hemodynamic coupling between aortic stiffening and peripheral arterial vessels and flow dynamics through an ETA-dependent mechanism. ETA receptor blockade may have therapeutic potential for improving peripheral vessel structure and function in the treatment of aortic stiffness-induced hypertension.
Highlights
Increased central arterial stiffness often precedes all-cause mortality and total cardiovascular events including aging, myocardial infarction, diabetes, atherosclerosis, heart failure, and stroke[1,2,3,4,5]
Twelve weeks of aortic non-constrictive restraint (NCR) and 3 weeks of BQ-123 treatment had no significant influences on body weights and heart rates as compared to sham
A non-constrictive restraint (NCR) created aortic stiffening in a rat model which leads to hypertension after 12 weeks
Summary
Increased central arterial stiffness often precedes all-cause mortality and total cardiovascular events including aging, myocardial infarction, diabetes, atherosclerosis, heart failure, and stroke[1,2,3,4,5]. The two major hypotheses considered in this study are: (1) Aortic stiffening results in structural and functional remodeling of peripheral small arteries and impaired regulation of local flow; and (2) Treatment with ETA receptor antagonist has beneficial effects on peripheral arterial remodeling and local flow pattern to normalize blood pressure. To test these hypotheses, an increase in aortic stiffness in a normal rat model was created by use of a non-constrictive restraint, NCR (glue coating) on the external surface of abdominal aorta. The chronic administration of the specific ETA receptor antagonist (BQ-123) was performed in aortic NCR animals
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