Vessel Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 371

The matching of oxygen supply with demand requires change in blood perfu-
sion upon sensing tissue oxygen need. The red blood capsule can sense oxygen
level and release ATP when oxygen content falls and its hemoglobin becomes
desaturated [ 687 ]. Intraluminal ATP is a vasodilator. In the blood vessel lumen,
ATP concentration increases during hypoxia [ 688 ]. Red blood capsules also secrete
ATP when exposed to increased temperature, reduced pH, hypercapnia, elevated
stresses and strains. Hypoxia supports the activation of K AT P channels that causes
hyperpolarization and vasodilation [ 690 ]. In arterioles of rat cremaster muscle that
possess both

α 1d- and α 2d-adrenergic receptors, the latter is functionnaly coupled

to K AT P channel; 2d-adrenoceptors inhibits and hypoxia activates K AT P channels.

In addition, augmented hemodynamic stresses on endothelial cells prime ATP
release into the vessel lumen [ 689 ]. Therefore, luminal ATP sources encompass
circulating red blood capsules and endothelial cells.
At perivascular sympathetic nerve endings, ATP is released as a cotransmitter
with noradrenaline. Messenger ATP then links to P2X 1 receptors on adjacent
smooth myocytes and launches vasoconstriction.

α

7.9.1 Extracellular ATP Processing

Extracellular ATP concentration is regulated by enzymes that degrade ATP to ADP,
AMP, and adenosine. The latter can binds to its cognate receptors, thereby regulating
the vascular tone. However, ATP can elicit signaling on vascular cells before its
catabolism, although ATP is rapidly and sequentially hydrolyzed to adenosine.
The degradation of ATP to AMP is catalyzed either by ectonucleotidases (ec-
tonucleotide triphosphate diphosphohydrolases ENTPD1-ENTPD6) or ectoapyrase
(ectonucleoside triphosphate diphosphohydrolase ENTPD1); 44 AMP is processed
to adenosine by ecto-5 -nucleotidase (Nt5E). The plasmalemmal, Ca 2 + -andMg 2 + -
dependent ectoenzyme ATPase on endothelial cells hydrolyzes extracellular ATP.
Membrane-bound ectonucleotidases process extracellular tri- (ATP and UTP) and
diphosphonucleosides (ADP and UDP). Cells also release soluble nucleotidases,
or exonucleotidases, into the extracellular medium. Therefore, especially ectonu-
cleotidases regulate the concentration of ATP both in the blood vessel lumen and
extracellular space surrounding vascular smooth myocytes, hence amounts of ATP
and its catabolites available for activation of receptors.

44 A.k.a. ectoATPase-1 and ectoATP diphosphohydrolase-1 (EATPD1).