Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of Ca1.2 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 channel (Ca1.2) 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/Ca1.2 channel in regulating cerebral artery function after exercise intervention.

RESULTS

Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased Ca1.2 activity and Ca influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle-specific AKAP150 knockin mice were hypertensive with higher Ca1.2 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 Ca1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. ATR (AT receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved ATR-AKAP150 association in myocytes of hypertension.

CONCLUSIONS

The current study demonstrates that aerobic exercise ameliorates Ca1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.