Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of Ca _V 1.2 Channel Function in Cerebral Arteries of Hypertensive Rats

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 (Ca V 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/Ca V 1.2 channel in regulating cerebral artery function after exercise intervention. RESULTS: Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased Ca V 1.2 activity and Ca 2+ influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle–specific AKAP150 knockin mice were hypertensive with higher Ca V 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 Ca V 1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle–specific AKAP150 knockin mice. AT 1 R (AT 1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II–involved AT 1 R-AKAP150 association in myocytes of hypertension. CONCLUSIONS: The current study demonstrates that aerobic exercise ameliorates Ca V 1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.