Calcium sensitization as a pharmacological target in vascular smooth-muscle regulation.
Numerous diseases have been associated with alteration(s) in smooth-muscle cell tone (ie, heightened contraction and/or diminished relaxation), including vascular disorders such as hypertension, cerebral vasospasm, coronary vasospasm and erectile dysfunction. Given the numerous steps that occur between receptor activation, signal transduction and cellular activation in vascular smooth muscle, it is not surprising that the etiology of common cardiovascular diseases/disorders is multifactorial. Nonetheless, this review will highlight the potential importance of the relationship between intracellular calcium levels and force generation, referred to as calcium sensitization, to these disease processes. As such, the complexities of the overlapping biochemical systems/pathways that govern calcium sensitization in vascular myocytes are reviewed, and the possibility that alterations in calcium sensitization may provide a common link among distinct vascular disorders is explored. A corollary of this supposition is that improved knowledge and understanding of the intrinsically complex regulation of calcium sensitization will provide novel opportunities for improved therapy of vascular disease.
Christ
George
G
Cell, Tissue and Organ Physiology Program, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27157, USA.
Wingard
Christopher
C
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D014652:Vascular Diseases / Q000188:drug therapy*; D014661:Vasoconstriction / Q000187:drug effects; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D009712:Nucleotides, Cyclic; D043562:Receptors, G-Protein-Coupled; D016718:Arachidonic Acid; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D002118:Calcium