Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 492

muscarinic M 3 receptors appears at higher concentrations. At relatively high doses,
its direct constrictor effect on smooth myocytes dominates over its vasodilator effect
on endothelial cells.
In fact, acetylcholine initiates 2 competing responses in mouse arteries: (1)
endothelium-dependent vasodilation mediated predominantly by nitric oxide and
(2) endothelium-dependent vasoconstriction mediated by thromboxane-A2 [ 902 ].
In atheromatous coronary arteries, vasoconstriction and -dilation occur at low
concentration and vasoconstriction happens at high concentrations. In 53% of
patients with normal coronary arteriograms, chest pain, and risk factors for coronary
artery disease, infusion of acetylcholine causes both constriction and dilation of
proximal and distal segments of epicardial coronary arteries [ 903 ]. Vasoconstriction
and -dilation coexist in different coronary arteries as well as in different segments
of a given artery (acetylcholine concentration range 10 − 7 -10 − 6 mol/l). In any case,
change in epicardial coronary artery caliber in response to acetylcholine does not
correlate with change in intramyocardial coronary blood flow.

9.5.5.2 Serotonin and Substance-P

Serotonin and substance-P are observed in endothelial cells [ 905 ]. 50 Atheromatous
arteries that constrict in response to acetylcholine may dilate upon exposure of
substance-P, an endothelium-dependent vasodilator, although dysfunction of the
endothelium action is not restricted to muscarinic receptors, but also to other recep-
tors such as tachykinin (substance-P) receptors [ 903 ]. In addition, the endothelial
response to chemical stimuli is not related to the degree of coronary atherosclerosis.

9.5.5.3 Adrenomedullin

Adrenomedullin is widespread, but at higher concentrations in endothelial cells
and vascular smooth myocytes. Adrenomedullin circulates in the plasma at pi-
comolar levels. Elevated plasma concentration of adrenomedullin occur during
pregnancy. Strongly vascularized tissues, such as the heart, lungs, and kidneys,
release adrenomedullin during inflammation, hypoxia, sepsis, and cardiovascular
diseases (myocardial infarction, heart failure, and atherosclerosis), particularly
during hypertension.
Adrenomedullin synthesis is regulated via estrogen-responsive elements
Adrenomedullin type and concentration vary according to the genetic ground,
especially gender, because the adrenomedullin gene is regulated by estrogen.

50 Levels of serotonin and substance-P are similar in endothelial cells of femoral and mesenteric
arteries of rats. Substance-P is also localized in endothelium of rat coronary arteries [ 904 ].