Increased aortic stiffness elevates pulse and mean pressure and 2 compromises endothelial function in Wistar rats

20 Articles in PresS. Am J Physiol Heart Circ Physiol (July 18, 2014). doi:10.1152/ajpheart.00265.2014 Copyright © 2014 by the American Physiological Society. An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to 21 determine the effect of increased aortic stiffness on PP and endothelial dysfunction as precursors to 22 hypertension. A rat model of suddenly increased aortic stiffness by use of a non-constrictive restraint 23 (glue coating) on aortic surface was created to investigate the change of PP and mean arterial pressure 24 (MAP). Group I (n=16) underwent aorta restraint for 4 weeks. Group II (n=12) underwent aortic 25 restraint for 4 weeks, followed by restraint removal to evaluate extent of reversibility for additional 4 26 weeks. The aortic and peripheral endothelial function was assessed by acetylcholine–stimulated 27 endothelium-dependent vasodilation. The level of nitrate/nitrite (NOx), endothelin-1 (ET-1) and 28 prostacyclin (PGI2) were measured in the serum and artery tissue. We found that aortic stiffening 29 causes a significant increase in PP and MAP (P<0.05). The endothelial function were markedly blunted 30 (P<0.05) in both aorta and small peripheral artery. After removal of the restraint, the impaired 31 endothelium function persisted in the aorta likely due to sustained deterioration of aortic wall, but was 32 partially restored in peripheral artery. The endothelial dysfunction was correlated with a decrease in 33 NOx and PGI2 (P<0.05) and an increase in ET-1 (P<0.05). Our results show that aortic stiffening results 34 in widening of PP which affected endothelium function through changes in synthesis of NOx, ET-1 and 35 PGI2. These findings suggest that increased aortic stiffness may be a cause of increased PP and a 36 precursor to hypertension. 37