Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 448

8.5.8.6 Vasoconstrictors

In addition to relaxing factors, endothelial cells can produce vasoconstrictors, such
as endothelin-1, superoxide anions [ 834 ], endoperoxides, and thromboxane-A2.
Some G-protein-coupled receptors on the surface of smooth myocytes re-
spond to vasoconstrictors, such as nucleotides or nucleosides and eicosanoids,
that are released locally from the endothelium or perivascular nerves as well as
circulating vasoconstricting hormones such as adrenaline. Other locally secreted
(generated and/or stored) vasoconstrictors include angiotensin-2 produced from its
precursor angiotensin-1, a cleavage product from angiotensinogen, in endothelial
cells; monoamine serotonin synthesized in enterochromaffin cells of the gut, then
stored in and released from platelets; and histamine released from mastocytes.
The sympathetic nervous system activates smooth muscle -adrenoceptors mainly

by releasing biogenic amine noradrenaline from perivascular nerves to constrict
blood vessels, especially small arteries that are responsible for systemic vasculature
resistance.

α

Nucleotides

Extracellular nucleotides, such as adenosine triphosphate (ATP), uridine di- (UDP)
and triphosphate (UTP), regulate pulmonary vasomotor tone via P2X and P2Y
receptors. The nucleotide uridine adenosine tetraphosphate (UP 4 A) vasoconstricts
likely via P2X 1 receptors (probably also P2Y 2 and P2Y 4 ). Stimulation by adenosine
triphosphate, uridine triphosphate, acetylcholine, endothelin, and mechanical stress
releases UP 4 A from endothelium [ 835 ]. Agent UP 4 A, UDP, and UTP are equipotent
in the endothelium-denuded artery, but UP 4 A is much more potent than UDP
and UTP in endothelium-intact vessels [ 836 ]. Vasoconstriction primed by UP 4 A
involves the entry of extracellular Ca 2 + and release of Ca 2 + from intracellular
stores.
Uridine triphosphate provokes actin polymerization via RoCK kinase that
suppresses activity of delayed rectifier K + channel, thereby facilitating depolariza-
tion and constriction of vascular smooth myocytes of cerebral arteries [ 837 ].
Adenosine triphosphate , quickly released by the endothelium when the flow
increases, is a vasoconstrictor that binds to the 2 P2X and P2Y purinergic receptor
types. However, ATP bound to endothelial P2X 1 receptors induces a constriction
followed by a vasodilation [ 838 ].

Bradykinin

Wall shear stress enhances bradykinin secretion [ 839 ]. Like nitric oxide and endo-
thelin, certain vasoactive substances, such as ATP, angiotensin-2, and substance-P,
can cause proliferation of endothelial and/or smooth myocytes.