The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.
Animal ; Estradiol/pharmacology* ; Female ; In Vitro ; Ovariectomy* ; Rats ; Rats, Sprague-Dawley ; Vasoconstrictor Agents/pharmacology* ; Vasodilator Agents/pharmacology* ; Vasomotor System/drug effects*

Objective: To assess the effect of combined hospital and home-based exercise programs on functional capacity and quality of life (QoL) among uncorrected atrial septal defect-associated pulmonary arterial hypertension (ASD-PAH) patients. Methods: This study was a randomized controlled trial with uncorrected ASD-PAH patients as the subjects. They were allocated randomly into control and exercise groups. Exercise group subjects performed hospital and home-based exercise programs, completing baseline 6-minute walking test (6MWT) and EQ-5D-3L QoL test (Utility Index and EQ-VAS scores), and were followed up for 12 weeks. The primary outcomes were 6MWT distance and EQ-5D-3L score at week 12. The N-terminal pro B-type natriuretic peptide (NT-proBNP) level was also assessed. A repeated-measure ANOVA was performed to detect endpoint differences over time. Results: The exercise group contained 20 subjects and control group contained 19. In total, 19 exercise group subjects and 16 control group subjects completed the protocol. The 6MWT distance, Utility Index score, and EQ-VAS score incrementally improved significantly in the exercise group from baseline until week 12, with mean differences of 76.7 m (p<0.001), 0.137 (p<0.001) and 15.5 (p<0.001), respectively. Compared with the control group, the exercise group had significantly increased 6MWT distance and utility index score at week 12. The EQ-VAS score increased in the exercise group at week 12. The NT-proBNP level decreased at week 12 in the exercise group. Conclusion Combined hospital and home-based exercise program added to PAH-targeted therapy, improving functional capacity and QoL in uncorrected ASD-PAH patients.