Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide

Abstract

. Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide. Am J Physiol Heart Circ Physiol 290: H1788 -H1797, 2006. First published November 23, 2005 doi:10.1152/ajpheart.01070.2005We have recently shown that estrogen causes vessel dilation through receptor-mediated stimulation of nitric oxide (NO) production. Here, we hypothesize that estrogen modulates the mechanical homeostasis in the blood vessel wall through NO production. The mechanical properties of female ovariectomized (ovx) mice, female mice lacking the gene for endothelial NO synthase (eNOS Ϫ/Ϫ ), and control female and male mice were studied to test the hypothesis. The femoral and carotid arteries and aorta were cannulated in situ and mechanically distended. The stress, strain, elastic modulus, and wall thickness of vessels in ovx and eNOS Ϫ/Ϫ mice, as well as intact female and male mice, were determined. Western blot and immunohistochemistry were used to assess eNOS protein expression in the aorta. Moreover, NO by-products of the femoral and carotid artery were determined by measuring the levels of nitrite and nitrate. Our results show that ovariectomy and eNOS Ϫ/Ϫ significantly decrease the strain in all arteries. Furthermore, the eNOS protein was significantly reduced in ovx mice. Finally, the NO metabolites were significantly decreased both in ovx and eNOS Ϫ/Ϫ mice. We found statistically significant correlations between the structural (wall thickness), mechanical (stress, strain, and elastic modulus), and biochemical parameters (NO by-products). These novel results connect NO to the structural and mechanical properties of the vessel wall. Hence, the effect of endogenous estrogen on the arterial mechanical properties is mediated by the regulation of NO derived from eNOS. nitrite; strain; stress; elastic modulus; ovariectomy THE MECHANICAL PROPERTIES of arteries are an important determinant of blood flow dynamics in the circulatory system because they determine the pressure-flow relation, wave reflection, and vessel dimension. Vascular remodeling leading to decreased distensibility has been described for a number of cardiovascular complications, including systemic hypertension (3), pulmonary hypertension (17), and atherosclerosis (34). In these disease states, arteries become stiffer with a loss of capacitance. Pourageaud et al. (30) reported an increase in elastic modulus of coronary artery but not in mesenteric resistance arteries in spontaneously hypertensive rats. Jiang et al. (14) found that risk factors for atherosclerosis were associated with alteration of mechanical forces, including low wall shear stress and high circumferential wall tension.Epidemiological studies have shown that the incidence of cardiovascular disease is higher in men than in premenopausal women but increases in postmenopausal women (5). The increase appears to be related to the diminishing concentration of female hormone that characterizes this stage (35). In contrast, the Women's Health Initiative (WHI) and the Heart and Estrog...

Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension

“…This finding is consistent with a previous study that showed that systemic arteries from OVX female mice were less compliant than those of intact female mice (8). We confirmed the impact of this compliance decrease in vivo by measuring pulmonary pressures in a subgroup of OVX mice treated with estrogen or placebo after 21 days of SuHx.…”

Laser 3D Printing with Sub‐Microscale Resolution of Porous Elastomeric Scaffolds for Supporting Human Bone Stem Cells

“…[ 47 ] Chondrocytes have been successfully cultured on alginate gels that are mechanically similar to cartilage with a Young's modulus at or greater than 75 kPa. [ 48 ] The Young's modulus of the photoelastomer evaluated in the present study could be modifi ed by altering the chemical composition; using the present formulation, the Young's modulus of 96 kPa was similar to that of skeletal muscle, [ 38 ] the spinal cord, [ 39 ] arteries, [ 40 ] and other tissues. [ 49 ] While the effects of stiffness are not necessarily required in static monolayer cell culture, a customized stiffness value is suitable for other biological applications such as use in mechanically dynamic culture or in implants; materials in these applications are subjected to repeated or cyclical mechanical stress.…”

“…The photoelastomer formulation described above with a value of 96 kPa was selected for further study due to the biomedical applicability of this material for regeneration of skeletal muscle, arteries, and other tissues. [38][39][40] …”

Relation of Nitrite to Structural and Mechanical Adaptation of Arteries During Postnatal Development

“…The data suggest that the strain and stress of the vessel showed a significant linear relation while the modulus of the vessel revealed an inverse relation with NO production. 11 Those data reflect a relationship between the endothelial function and the mechanical property of the femoral and carotid arteries of the adult male, female, ovariectomized and eNOS -/-female mice. Similar findings were made in coronary arteries of control mice and those exposed to cigarette smoke.…”

“…Recently, Guo et al have shown significant correlation between nitrite and vessel wall thickness, strain, stress and elastic modulus under the influence of estrogen 11 in femoral arteries and cigarette smoke in coronary artery 12 of mice. In a postnatal model, Huang et al 14 investigated the axial variations of geometry (diameter and length), and mechanical properties (stress-stain relation, elastic modulus and compliance) of the C57BL mice aorta from the aortic valve to the common iliac.…”