1. Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of Ca V 1.2 Channel Function in Cerebral Arteries of Hypertensive Rats.
- Author
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Zhang Y, Xu Z, Shan M, Cao J, Zhou Y, Chen Y, and Shi L
- Subjects
- Animals, Male, Physical Conditioning, Animal physiology, Protein Kinase C-alpha metabolism, Protein Kinase C-alpha genetics, Calcium Signaling, Mice, Inbred C57BL, Mice, Rats, Rats, Inbred WKY, Angiotensin II, Blood Pressure, Signal Transduction, A Kinase Anchor Proteins metabolism, A Kinase Anchor Proteins genetics, Calcium Channels, L-Type metabolism, Calcium Channels, L-Type genetics, Rats, Inbred SHR, Hypertension physiopathology, Hypertension metabolism, Hypertension genetics, Cerebral Arteries metabolism, Cerebral Arteries physiopathology, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular physiopathology, Myocytes, Smooth Muscle metabolism, Disease Models, Animal
- 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 Ca
2+ channel (CaV 1.2) 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/CaV 1.2 channel in regulating cerebral artery function after exercise intervention., Results: Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased CaV 1.2 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 CaV 1.2 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 CaV 1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. AT1 R (AT1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved AT1 R-AKAP150 association in myocytes of hypertension., Conclusions: The current study demonstrates that aerobic exercise ameliorates CaV 1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension., Competing Interests: Disclosures None.- Published
- 2024
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