Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Abstract

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects - and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.

Keywords: Adrenergic receptors; calcium channel; calcium channel blocker; neurovascular unit; vasopressor.

Figure 1.

Neurovascular anatomy and its associated components. A visual representation of the neurovascular anatomy provided here in a longitudinal-and-cross sectional fashion along pial and penetrating arterioles, capillary, and venule. Arterioles comprise of a thick coat of smooth muscle cells, which become thinner and are replaced by pericytes as the vessel transitions into a capillary. A thin layer of smooth muscle cells reappear as capillaries transition into venules. A continuous endothelial cell layer, as well as a neural innervation is present along the vascular transition from penetrating arteriole to venule.

Figure 2.

Schematic description of subtypes, distribution, and density of adrenoceptors and calcium channels along the cerebrovascular tree. Distribution and density of adrenoceptor subtypes and calcium channels depicted by color and column height along principal cerebral vessels, respectively (Figure Legend and insets). Also shown is the cell-specific localization of adrenoceptor subtypes and calcium channels.