Abstract
Background: The effect of hormone replacement therapy on vascular disease has been controversial. The purpose of this study was to determine the effect of progesterone and estrogen on vasomotor function in a porcine coronary artery model. Methods: Porcine coronary artery rings were incubated as controls or with progesterone, estrogen or a combination of the two. After culturing for 24 hrs, the rings were tested on a myograph tension system to measure contraction and relaxation in response to U46619 and bradykinin or sodium nitroprusside (SNP), respectively. Nitric oxide synthase (eNOS) mRNA and protein levels were determined by RT-PCR and western blot, respectively. Levels of superoxide radical were determined by lucigenin enhanced chemiluminescence assay. Results: In response to 10–7M bradykinin, porcine coronary artery rings treated with 5 ×10−5, 1 × 10–5 and 1 × 10–6M of progesterone showed a significant reduction of endothelium-dependent vasorelaxation by 68%, 45%, and 36% respectively, as compared to controls (P < 0.05). However, the rings treated with estrogen showed no significant difference as compared to controls. Furthermore, estrogen treatment with progesterone reversed the effect of progesterone, showing no difference of vessel relaxation as compared to controls. There were no differences in endothelium-independent vasorelaxation (SNP) or in smooth muscle contractility (U46619) between control and hormone-treated groups. The eNOS mRNA and protein levels did not show any changes in progesterone or estrogen treated vessels. Porcine coronary endothelium exposed to progesterone showed a 59% increase in superoxide anion production while estrogen decreased superoxide anion by 67% when compared to controls (P < 0.05 for both). Conclusions: These data demonstrate that progesterone has a detrimental influence on endothelium-dependent relaxation. This effect may be due to increased consumption of NO by superoxide free radicals in the endothelium of tissues exposed to progesterone. By contrast, estrogen may provide a beneficial effect on maintaining endothelium function and reducing oxidative stress.
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