Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training

Abstract

The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (≈13%–41%; P <0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F 1a ). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased ( P <0.05) the vasodilator response to epoprostenol (≈100%–150%) and acetylcholine (≈100%–120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women.

Cardiac Adaptations to High‐Intensity Aerobic Training in Premenopausal and Recent Postmenopausal Women: The Copenhagen Women Study

“…The training sessions were characterized by ≈50 minutes of intermittent high‐intensity intervals where the participants reached HRs over 85% of maximum HR (Table ). For more information and details on the participants’ variation in exercise intensities during the training see Nyberg et al and Mandrup et al …”

“…However, the role of age versus hormonal changes for cardiovascular risk after menopause in women remains debated, in part because of the fact that comparisons of premenopausal and postmenopausal women are often conducted with significant age differences between the groups . We and others have recently provided support for the notion that the menopausal transition per se leads to rapid impairments in vascular function . In Nyberg et al, 7 leg vascular function, assessed by infusion of vasoactive compounds, was markedly impaired in recent postmenopausal women compared with age‐matched premenopausal women.…”

An Ecosystem to Support Traditional Clinical Investigation

“…Consistent with these concerns, leading bioinformatics experts are now openly warning about the limited ability of electronic health records to capture and provide research grade phenotypic data. 11 In conclusion, Nyberg et al 1 show the ongoing power of deep phenotyping and mechanistic studies in human subjects. The novel observations related to blood pressure, vascular biology, menopause, and exercise training in women from this study also make the larger case for continued support of the people and infrastructure critical for such deep phenotyping studies in humans.…”

“…The list of questions goes on and on. So although Nyberg et al 1 show that the resistance vessels of younger postmenopausal do in fact respond to exercise training, many questions remain about the integrative responses to exercise training that influence blood pressure in this demographic group. In addition, will older postmenopausal women respond similarly to younger postmenopausal women?…”

“…See related article, pp 1011-1020 I n this edition of Hypertension, Nyberg et al 1 from the University of Copenhagen report that both prostacyclin-and acetylcholine-induced vasodilation are blunted in the legs of young (mean age, 54 years) postmenopausal women and subsequently improved by endurance exercise training. At first glance, this is a terrific piece of mechanistic physiology and high resolution or deep phenotyping combined with an exercise training intervention in humans.…”