Submitted on October 11, 2005
Accepted on November 16, 2005
Estrogen Modulates the Mechanical Homeostasis of Mouse Arterial Vessels through Nitric Oxide
Xiaomei Guo1, Xiao Lu1, Huimin Ren2, Ellis Levin3, and Ghassan S Kassab1*
1 Biomedical Engineering, University of California, Irvine, Irvine, CA, USA
2 Institue of Neurology, Medical Center of Fudan University, Shanghai, China
3 Department of Medicine, University of California, Irvine, Irvine, CA, USA
* To whom correspondence should be addressed. E-mail: gkassab{at}uci.edu.
We 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-/-) and control female and male mice were studied to test the hypothesis. The femoral, 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-/- mice as well as intact female and male mice were determined. Western blot and immunhistochemistry were used to assess eNOS protein expression in the aorta. Moreover, NO byproducts of the femoral and carotid artery were determined by measuring the levels of nitrite and nitrate. Our results show that ovariectomy and eNOS-/- 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-/- mice. We found statistically significant correlations between the structural (wall thickness), mechanical (stress, strain, elastic modulus) and biochemical parameters (NO byproducts). These novel results connect NO to the structural and mechanical properties of the vessel wall. Hence, the mechanism of endogenous estrogen effect on the arterial mechanical properties is related to the regulation of NO derived from eNOS.
