CARDIOVASCULAR PHYSIOLOGY CONCEPTS
■ FIGURE 7.1 Vasoactive substances derived from tissue cells around arterioles. Increased tissue m etabo-
lism leads to form ation of metabolites that dilate ( -) nearby arterioles. Increased oxygen consumption
decreases the tissue partial pressure of oxygen
which dilates arterioles. Some cells release locally
acting, paracrine hormones (or their precursors), which can either constrict (+) or dilate (-) arterioles.
carbon dioxide; K+, potassium ion; H+, hydrogen ion.
different cell types surrounding blood vessels
can release vasoactive substances referred to
as local, paracrine hormones (e.g., histamine,
bradykinin, and prostaglandins). A paracrine
horm one is a substance released by one cell
that acts on another nearby cell by diffusing
through the interstitial fluid. This is in con-
trast to endocrine hormones that circulate
in the blood to reach distant target cells or
autocrine substances that affect the same cell
from which they are released.
Increases or decreases in metabolism alter
the release of some of these vasoactive sub-
stances; thus, metabolic activity is closely
coupled to blood flow in most organs of the
For example, an increase in tissue
metabolism, as occurs during muscle contrac-
tion or during changes in neuronal activity in
the brain, leads to an increase in blood flow.
Extensive evidence shows that the actively
release vasoactive substances that cause vaso-
dilation. This is termed the metabolic theory
of blood flow regulation. These vasoactive
substances, which are linked to tissue metab-
olism, ensure that the tissue is adequately
supplied with oxygen and that products of
metabolism (e.g., CO2, H+, lactic acid) are
removed. Several substances have been impli-
cated in metabolic regulation of blood flow.
Their relative importance depends on the tis-
sue in which they are formed as well as differ-
ent conditions that might cause their release.
most organs (although adenosine constricts
renal vessels). It is formed by the action of
5,-nucleotidase, an enzyme that dephos-
(AMP). The AMP is derived from hydroly-
sis of intracellular adenosine triphosphate
(ATP) and adenosine diphosphate (ADP).
hypoxia and increased oxygen consump-
both of which lead to
ATP hydrolysis. Small amounts of ATP
hydrolysis can lead to large increases in
adenosine formation because intracellular
concentrations of ATP are about a 1000-
fold greater than adenosine concentrations.
Experimental evidence supports the idea
that adenosine formation is a particularly
important mechanism for regulating coro-
nary blood flow when myocardial oxygen
consumption increases or during hypoxic
2. Inorganic phosphate is released by the
hydrolysis of adenine nucleotides (ATP,
may have some vasodilatory activity in