Sex hormones and aortic wall remodeling in an arteriovenous fistula

Background: An arteriovenous fistula (AVF) creates high blood flow through the artery and fistula. With this high flow, there is flow-induced remodeling and an increase in diameter, but no intimal hyperplasia. Estrogen has been shown to modify vascular remodeling, decreasing intimal hyperplasia after endothelial injury. Objective: These experiments tested the hypothesis that estrogen administration would decrease wall thickness in an AVF model. Because estrogen may decrease wall thickness, we also tested the hypothesis that testosterone would increase wall thickness. Methods: A fistula was created between the abdominal aorta and the inferior vena Cava in Sprague-Dawley rats to generate high blood flow conditions in the aorta. Four groups of female animals were examined: sham, control with AVF, ovariectomized (OVX) with AVF, and OVX plus testosterone with AVF. Four groups of male animals were also examined: sham, control with AVF, castrated with AVF, and castrated plus estrogen with AVE Five weeks after creation of the AVF, the aortas were collected and fixed; wall thickness was measured both proximal and distal to the AVF. Results: Ovariectomy resulted in a significant decrease in estrogen levels (P < 0.01). Testosterone administration tended to increase testosterone levels in the OVX females, but values did not approach levels observed in the control males. No difference was noted in the proximal wall thickness between the control and the OVX animals. The OVX females receiving testosterone exhibited a significant increase in both proximal and distal wall thickness compared with control females (P < 0.001). In the male animals, there was no significant change in aortic wall thickness in the castrated rats compared with the controls. Estrogen administration in the castrated males resulted in a significant decrease in wall thickness in the proximal and distal aorta (P < 0.05). Conclusion: These studies suggest that, in a model of vascular remodeling, estrogen administration decreases wall thickness, and testosterone administration increases wall thickness. (Gend Med. 2007;4:157-169) Copyright (C) 2007 Excerpta Medica, Inc.