Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of CaV1.2 Channel Function in Cerebral Arteries of Hypertensive Rats.
Arterioscler Thromb Vasc Biol
; 44(6): 1202-1221, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38602101
ABSTRACT
BACKGROUND:
Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism by which myocyte AKAP150 (A-kinase anchoring protein 150) inhibition induced by exercise training alleviates voltage-dependent L-type Ca2+ channel (CaV1.2) activity and restores cerebral arterial function in hypertension.METHODS:
Spontaneously hypertensive rats and newly generated smooth muscle-specific AKAP150 knockin mice were used to assess the role of myocyte AKAP150/CaV1.2 channel in regulating cerebral artery function after exercise intervention.RESULTS:
Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased CaV1.2 activity and Ca2+ influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle-specific AKAP150 knockin mice were hypertensive with higher CaV1.2 channel activity and increased vascular tone. Furthermore, treatment of Ang II (angiotensin II) resulted in a more pronounced increase in blood pressure in smooth muscle-specific AKAP150 knockin mice. Exercise training significantly reduced arterial myocyte AKAP150 expression and alleviated CaV1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. AT1R (AT1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved AT1R-AKAP150 association in myocytes of hypertension.CONCLUSIONS:
The current study demonstrates that aerobic exercise ameliorates CaV1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ratos Endogâmicos SHR
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Artérias Cerebrais
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Canais de Cálcio Tipo L
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Miócitos de Músculo Liso
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Modelos Animais de Doenças
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Proteínas de Ancoragem à Quinase A
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Hipertensão
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article