Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner
| Autor: | Mallikarjuna R. Pabbidi, Tanya Pareek, Srinivas Sriramula, Joseph Reed |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty BK channel Aging Middle Cerebral Artery Vascular smooth muscle Physiology Large-Conductance Calcium-Activated Potassium Channel beta Subunits Protein subunit Ovariectomy Cerebral arteries Vascular Remodeling Constriction Membrane Potentials Rats Sprague-Dawley Sex Factors Downregulation and upregulation Physiology (medical) Internal medicine medicine.artery medicine Animals Arterial Pressure Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Messenger RNA biology Chemistry Age Factors Endocrinology Vasoconstriction Cerebrovascular Circulation Middle cerebral artery biology.protein Female Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Cardiovascular research. 116(7) |
| ISSN: | 1755-3245 |
| Popis: | Aims The myogenic reactivity of the middle cerebral arteries (MCA) protects the brain by altering the diameter in response to changes in lumen pressure. Large conductance potassium (BK) channels are known to regulate the myogenic reactivity, yet, it is not clear how aging alters the myogenic reactivity via the BK channel in males and females. Thus, we hypothesize that age-associated changes in BK channel subunits modulate the myogenic reactivity in a sex-specific manner. Methods and results We used vascular reactivity, patch-clamp, and biochemical methods to measure myogenic reactivity, BK channel function, and expression, respectively in cerebral vessels of adult and aged male and female Sprague Dawley rats. Our results suggest that aging and ovariectomy (OVX) exaggerated the myogenic reactivity of MCA in females but attenuated it in males. Aging induced outward eutrophic remodelling in females but inward hypertrophic remodelling in males. Aging decreased total, Kv, BK channel currents, and spontaneous transient outward currents (STOC) in vascular smooth muscle cells isolated from females, but not in males. Aging increased BKα subunit mRNA and protein both in males and females. However, aging decreased BKβ1 subunit protein and mRNA in females only. In males, BKβ1 mRNA is increased, but protein is decreased. Iberiotoxin-induced MCA constriction is lower in aged females but higher in aged males. Activation of BKα (10 µM NS1619) and BKβ1 (10 µM S-Equol) subunits failed to increase STOCs and were unable to decrease the myogenic reactivity of MCA in aged female but not in aged male rats. OVX decreased, but chronic supplementation of oestradiol restored BK channel expression and function. Conclusion Overall our results suggest that aging or OVX-associated downregulation of the BKβ1 expression and function in females results in exaggerated myogenic reactivity of MCA. However, age-associated increase in BK channel function in males attenuated myogenic reactivity of MCA. |
| Databáze: | OpenAIRE |
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