262
J. C. B. Jacobsen and C. Aalkjær
The arterial wall has three layers. An inner layer, which mainly consist of a single
cell layer—the endothelial cells. The endothelial cells separates the other layers of
the arterial wall from the blood, and produce a large number of molecules, which
are important for the fluidity of the blood and for the tone of the vascular smooth
muscle cells. The latter are present in the next layer of the arterial wall, the medial
layer. The smooth muscle cells of the medial layer are circumferentially oriented
and controls the lumen diameter and the compliance of the arterial wall through
contraction and relaxation. The third layer is the adventitia, which is a connective
tissue layer containing only few cells of importance for maintenance of the collagen
and elastic fibers and for some immune functions of the arterial wall. The inner part of
the adventitia (next to the smooth muscle cells of the media) harbors different types
of nerve fibers. The activity in the nerve fibers controls the tone of the smooth muscle
cells, i.e. some nerve fibers release substances, which causes contraction, while other
fibers release substances that relax the smooth muscle cells. Vasoactive substances
both from the endothelium and from the nerves thus affect the tone of the smooth
muscle cells. In addition, molecules produced in the various organs of the body
influence tone; a prominent example of this is the relaxant and hence vasodilatory
effect of metabolic end-products such as e.g. CO 2 .
The tone of the smooth muscle cells and hence the diameter of the arteries has
a number of hemodynamical consequences. By constriction and thus reduction of
vessel diameter the resistance to flow increases. By constricting some arteries and
dilating others, the blood can be shunted away from one organ or region and towards
another. Simultaneous constriction of a large number of arteries will also increase
the total hydraulic resistance, which means that the blood pressure, i.e. the pressure
in the large arteries at the level of the heart, increases. Finally, constriction of an
artery will reduce the intravascular pressure in the arteries, arterioles and capillaries
downstream for the constricted artery.
Arteries are conveniently divided into large and small arteries. The main function
of the large arteries is to dampen the oscillations in pressure and flow, which is
consequent to the pulsative action of the heart. The systole is the constriction phase
of the heart muscle when blood is expelled and pressure in the arterial system rises,
and the diastole is the filling phase, where the heart muscle is relaxed and arterial
pressure is lower.
The small arteries (and the even smaller arterioles) is where the main hydraulic
resistance resides and it is the regulation of the tone of the smooth muscle cells in
the small arteries that is important for the distribution of blood and for control of
blood pressure and capillary pressure. It is the small arteries, which are in focus in
this review.
The tone of the vascular smooth muscle cells is controlled by (1) the electrical
potential across the membrane (the membrane potential), (2) the release of Ca
2+ from
Ca
2+ -stores in the cells, and (3) the sensitivity of the contractile proteins to Ca
2+ .
The membrane potential is generated by a combination of active transport (transport
against an electrochemical gradient) of ions and passive transport of ions. The most
relevant ions are Na
+ , K
+ , and Cl
− . In a relaxed smooth muscle the membrane potential is about −60 to −80 mV, with the inside being negative. When the membrane
J. C. B. Jacobsen and C. Aalkjær
The arterial wall has three layers. An inner layer, which mainly consist of a single
cell layer—the endothelial cells. The endothelial cells separates the other layers of
the arterial wall from the blood, and produce a large number of molecules, which
are important for the fluidity of the blood and for the tone of the vascular smooth
muscle cells. The latter are present in the next layer of the arterial wall, the medial
layer. The smooth muscle cells of the medial layer are circumferentially oriented
and controls the lumen diameter and the compliance of the arterial wall through
contraction and relaxation. The third layer is the adventitia, which is a connective
tissue layer containing only few cells of importance for maintenance of the collagen
and elastic fibers and for some immune functions of the arterial wall. The inner part of
the adventitia (next to the smooth muscle cells of the media) harbors different types
of nerve fibers. The activity in the nerve fibers controls the tone of the smooth muscle
cells, i.e. some nerve fibers release substances, which causes contraction, while other
fibers release substances that relax the smooth muscle cells. Vasoactive substances
both from the endothelium and from the nerves thus affect the tone of the smooth
muscle cells. In addition, molecules produced in the various organs of the body
influence tone; a prominent example of this is the relaxant and hence vasodilatory
effect of metabolic end-products such as e.g. CO 2 .
The tone of the smooth muscle cells and hence the diameter of the arteries has
a number of hemodynamical consequences. By constriction and thus reduction of
vessel diameter the resistance to flow increases. By constricting some arteries and
dilating others, the blood can be shunted away from one organ or region and towards
another. Simultaneous constriction of a large number of arteries will also increase
the total hydraulic resistance, which means that the blood pressure, i.e. the pressure
in the large arteries at the level of the heart, increases. Finally, constriction of an
artery will reduce the intravascular pressure in the arteries, arterioles and capillaries
downstream for the constricted artery.
Arteries are conveniently divided into large and small arteries. The main function
of the large arteries is to dampen the oscillations in pressure and flow, which is
consequent to the pulsative action of the heart. The systole is the constriction phase
of the heart muscle when blood is expelled and pressure in the arterial system rises,
and the diastole is the filling phase, where the heart muscle is relaxed and arterial
pressure is lower.
The small arteries (and the even smaller arterioles) is where the main hydraulic
resistance resides and it is the regulation of the tone of the smooth muscle cells in
the small arteries that is important for the distribution of blood and for control of
blood pressure and capillary pressure. It is the small arteries, which are in focus in
this review.
The tone of the vascular smooth muscle cells is controlled by (1) the electrical
potential across the membrane (the membrane potential), (2) the release of Ca
2+ from
Ca
2+ -stores in the cells, and (3) the sensitivity of the contractile proteins to Ca
2+ .
The membrane potential is generated by a combination of active transport (transport
against an electrochemical gradient) of ions and passive transport of ions. The most
relevant ions are Na
+ , K
+ , and Cl
− . In a relaxed smooth muscle the membrane potential is about −60 to −80 mV, with the inside being negative. When the membrane