Systemic nimodipine affects pericyte calcium signaling, resting hemodynamics and neurovascular coupling in healthy mouse brain.

Nimodipine is a L-type voltage gated calcium channel blocker commonly given to patients after a sub-arachnoid hemorrhage. It is known to dilate cerebral arteries and affect brain pericytes that express voltage gated calcium channels. Here, we systemically administered nimodipine (1 ​mg/kg; i.p.) and measured brain pericyte calcium transients and single-vessel hemodynamics in the brains of mice by two-photon microscopy. We find that nimodipine reduces calcium transients in all types of pericytes, from ensheathing to thin-strand cells, at different locations in the vascular network. This induces local vasodilation of vessels closer to penetrating arterioles but decreases blood cell velocity. These vascular consequences are due to systemic nimodipine effects because direct brain application of nimodipine caused blood cell velocity to increase. Nimodipine treatment also reduced further dilation during neurovascular coupling throughout the vascular network. Overall, this suggests that nimodipine can change cerebrovascular hemodynamics by altering pericyte physiology and these are important considerations for the clinical use of this drug.