Figure 2
Modulators of vascular contractility. This is a schematicrepresentation of the main regulatory pathways of vascularsmooth muscle contraction, based on Brewster et al.[12, 72]. Creatine kinase (CK) is colocalized withCa2+ ATPase and myosin ATPase, and evidencesuggests the enzyme is also colocalized with myosin light chain(LC) kinase, to rapidly supply these enzymes with ATP usingcreatine phosphate (Creatine ~ P) [11, 12, 72, 88–90]. The guanidino compounds creatine and nitric oxide(NO) have a common precursor in L-Arginine [12]. NO, RhoA/Rho kinase, and calcium-dependent pathwaysare intracellular effectors of blood pressure-regulating systemsthat converge on metabolic processes fueled by CK [11, 12, 72, 88–91, 93–95]. CK is high in persons of African ancestry [11, 12, 72, 73], and this is thought to lead to greater contractilityof vascular smooth muscle [11, 12, 72]. Vascular contractile responses can be reducedthrough enhancing NO-dependent pathways, including with ACEinhibitor (ACE-i) or nebivolol-induced NO synthesis, or throughindirect inhibition of CK-dependent pathways, as with calciumblockers (CaB) or β-adrenergic agonists. Calcium blockersmay block the entry of calcium in the cell as well as theoutflow from the sarcoendoplasmic reticulum (SER) [93]. β-adrenergic agonists reduce contractilitymainly through inhibition of myosin light chain kinase [91]. β-adrenergic blockers antagonize thisbeneficial effect, which may help explain the more frequentoccurrence of blood pressure increase with β-blockers inpersons of African ancestry [3, 92], within the context of the greater vascularcontractility in this population subgroup [11, 12, 36, 37, 39, 72]. cGMP, guanosine cyclic3′,5′-(monophosphate); MLCP, myosin light chainphosphatase.