title: Osteopenia and endothelin-1-mediated vasconstrictor tone in postmenopausal women.
abstract: Low bone mineral density is highly prevalent in postmenopausal women. Osteopenia in postmenopausal women is a predictor of adverse cardiovascular events. A potential mechanism contributing to the increased cardiovascular risk in postmenopausal women with osteopenia is endothelial vasomotor dysfunction. Endothelin (ET)-1 is a potent vasoconstrictor peptide that is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Currently, there is no information on osteopenia and ET-1 vasoconstrictor activity in postmenopausal women. We tested the hypothesis that ET-1 mediated vasoconstrictor activity is greater in postmenopausal women with osteopenia compared with those without. Forearm blood flow responses to intra-arterial infusion of BQ-123 (100 nmol/min for 60 min), a selective ET(A) receptor antagonist, were determined in postmenopausal women: 10 with osteopenia (age: 56+/-1 yr, lumbar spine T-score between -1.5 and -2.5) and 12 without osteopenia (age: 60+/-2 yr, T-score>-1.5). In women with osteopenia, forearm blood flow increased approximately 25% (P<0.05) in response to BQ-123. However, in the women without osteopenia, resting forearm blood flow was not significantly changed. In conclusion, these results suggest that osteopenia is associated with greater ET-1-mediated vasoconstrictor tone. Increased ET-1 vasoconstrictor activity may contribute to the elevated cardiovascular risk in postmenopausal women with osteopenia.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mestek
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Christian M
authors.initials: CM
authors.lastname: Westby
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017698:Postmenopause; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D014662:Vasoconstrictor Agents; C072247:cyclo(Trp-Asp-Pro-Val-Leu)