Vascular Smooth Muscle and Tone

Vascular smooth muscle cells form the muscular layer of arteries and veins, and their sustained partial contraction — vascular tone — sets the caliber of the vessel and therefore the resistance to flow and the distribution of blood. Unlike the brief twitches of skeletal muscle, vascular smooth muscle holds graded, economical contractions for long periods under combined neural, hormonal, endothelial, and local metabolic control.

Definition

Vascular smooth muscle is the involuntary muscle of the vessel wall whose graded, sustained contraction (vascular tone) regulates vessel diameter; vascular tone is the level of constriction maintained relative to the fully relaxed state.

Scope

This topic covers the contractile machinery of vascular smooth muscle, the calcium-dependent and calcium-sensitization pathways that regulate contraction and relaxation, the maintenance of resting (basal) tone, and the plasticity of the smooth-muscle phenotype. It does not cover specific vasodilator or vasoconstrictor drug regimens.

Core questions

• How does calcium trigger and regulate vascular smooth-muscle contraction?
• What is calcium sensitization and how does it sustain tone economically?
• How do neural, hormonal, endothelial, and metabolic signals set resting tone?
• How does the smooth-muscle phenotype switch between contractile and synthetic states?

Key concepts

• Myosin light-chain phosphorylation
• Calcium-calmodulin-myosin light-chain kinase pathway
• Calcium sensitization and myosin light-chain phosphatase
• RhoA/Rho-kinase signalling
• Basal (resting) vascular tone
• Myogenic response
• Contractile versus synthetic phenotype switching

Key theories

Calcium sensitization of the contractile apparatus

Beyond raising intracellular calcium, agonists modulate the sensitivity of the contractile machinery to calcium by regulating myosin light-chain phosphatase, largely through the RhoA/Rho-kinase pathway, allowing sustained force at a given calcium level and economical maintenance of tone.

Mechanisms

Contraction begins when a rise in intracellular calcium binds calmodulin, activating myosin light-chain kinase, which phosphorylates the regulatory myosin light chain and permits cross-bridge cycling. Relaxation follows dephosphorylation by myosin light-chain phosphatase. Crucially, agonists can change the sensitivity of this system to calcium: signalling through RhoA and Rho-kinase inhibits the phosphatase, so force is sustained at a given calcium concentration — calcium sensitization — which lets vessels hold tone economically (Somlyo & Somlyo, 2003; Somlyo & Somlyo, 1994; Loirand et al., 2006). Resting tone reflects the balance of constrictor and dilator inputs, including sympathetic activity, circulating and local mediators, endothelial signals, and the myogenic response of small arteries to pressure (Mulvany & Aalkjaer, 1990). Vascular smooth muscle cells are also plastic, switching between a contractile and a synthetic phenotype during growth and disease (Owens et al., 2004).

Clinical relevance

Vascular tone is the proximate determinant of vascular resistance, and the pathways described here are the targets of many vasoactive influences. This entry explains the physiology as reference material and does not describe drug dosing or individualised treatment.

Evidence & guidelines

The contractile and calcium-sensitization mechanisms rest on classic smooth-muscle physiology (Somlyo & Somlyo, 1994, 2003) and on reviews of Rho-kinase signalling (Loirand et al., 2006); phenotype plasticity is synthesised in Owens et al. (2004), and small-artery structure-function in Mulvany & Aalkjaer (1990).

History

Early smooth-muscle physiology established calcium-calmodulin-dependent myosin light-chain phosphorylation as the contractile trigger. The recognition in the 1990s that agonists also modulate calcium sensitivity through myosin phosphatase, and the later identification of the RhoA/Rho-kinase pathway, reframed how sustained vascular tone is maintained (Somlyo & Somlyo, 1994, 2003; Loirand et al., 2006). Parallel work established that vascular smooth muscle cells are not terminally fixed but switch phenotype during development and disease (Owens et al., 2004).

Key figures

• Andrew P. Somlyo
• Avril V. Somlyo
• Gary K. Owens
• Michael J. Mulvany

Seminal works

• somlyo-somlyo-2003
• owens-2004
• mulvany-aalkjaer-1990

Frequently asked questions

What is vascular tone?

It is the level of sustained partial contraction that vascular smooth muscle maintains, which sets the vessel's diameter relative to its fully relaxed state and therefore its resistance to flow.

What is calcium sensitization?

It is the process by which signalling pathways increase the contractile machinery's response to a given amount of calcium, mainly by inhibiting myosin light-chain phosphatase, allowing tone to be sustained economically.