The goal of this survey was to review briefly the molecular mechanisms that regulate vascular smooth muscle function. Components of the machinery involved in the contraction and relaxation of vascular smooth muscle include the following. Contractile proteins. The force generated by vascular smooth muscle is the result of thin (actin) and thick (myosin) filaments being pulled by one another so that the cell tends to shorten. The processes by which this intereaction is regulated are a matter of some debate. However, most observations indicate that the process that initiates contraction is a calcium-dependent phosphorylation of the myosin light chain. Cellular sites for the regulation of myoplasmic calcium concentration. The final event that initiates the contractile process is an increase in the intracellular concentration of ionized calcium. Cellular sites that may contribute to the raising and lowering of ionized calcium include the following: (A) cell membrane, (B) sarcoplasmic reticulum, and (C) mitochondria. Membrane electrical events. The electrical state of the cell membrane influences contractile responses of vascular smooth muscle. Over the physiologic range, an elevation in the membrane potential has a reciprocal influence on muscle excitability. The membrane potential is the sum of the diffusion potentials and the electrogenic pump. Excitation-contraction coupling. The excitatory events of the cell membrane (changes in membrane potential and the generation of action potentials) are coupled to the interaction of the contractile proteins by an increase in myoplasmic ionized calcium. Cyclic nucleotides and calcium. Cyclic AMP and cyclic GMP may link contraction and relaxation to the release and uptake of activator calcium by subcellular organelles. These nucleotides also influence the level of phosphorylation of the myosin light chain. Energy metabolism and hypoxia. The chemical energy source for cellular processes in vascular smooth muscle is ATP. Vascular tone, or maintenance of a contractile force, in this muscle is a relatively efficient process that may reflect a special noncycling link between myosin and actin. Current evidence suggests that hypoxic conditions influence vascular tone by altering the activity of the electrogenic sodium pump. This listing of statements is by no means the final word in molecular mechanisms that govern vascular tone. Indeed, vascular smooth muscle remains to be a constant source of surprises for the interested investigator.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine