Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 445

-hydroxylase
generates 20-hydroxyeicosatetraenoic acid from arachidonic acid. Signaling medi-
ated by 20HETE is activated by endothelin-1 and angiotensin-2. Vasoconstriction
caused by 20HETE, an antagonist to Ca 2 + -activated K + channel, is attenuated by
epoxyeicosatrienoic acids, agonists of Ca 2 + -activated K + channel.
Products of cytochrome-P450 epoxygenase and

In smooth myocytes, after calcium influx, cytochrome-P450 ω

-hydroxylase as well as reac-
tive oxygen species derived from NADPH are intracellular signal transducers for
proliferation of vascular cells (via extracellular-regulated protein kinase-1 and -2)
as well as angiogenesis.
In the kidney, epoxyeicosatrienoic acids decrease sodium excretion and renin
release. The cerebral blood flow is regulated by the antagonistic effects of EET
and 20HETE, EETs being produced by adjoining astrocytes. 20HETE can reduce
the vascular tone and dilate pulmonary arteries [ 824 ]. Agent 20HETE lowers
the pulmonary vasoconstriction due to hypoxia. Effects of EETs (vasodilation or
constriction) on pulmonary vessels vary according to mechanical and chemical
environment.
In vascular endothelial cells subjected to acetylcholine, bradykinin, and shear
stress, activated phospholipases produce arachidonic acid that is processed by
cyclooxygenases, cytochrome-P450s, and lipoxygenases. In vascular endothelium
of some arteries, a substantial component of vasodilation depends on lipoxygenase-
induced arachidonic acid metabolites. Arachidonate 15-lipoxygenase (ALOx15)
synthesizes vasoactive metabolites such as 15-hydroxy (11,12)-epoxyeicosatrienoic
acid that is hydrolyzed by soluble epoxide hydrolase to (11,12,15)-trihydroxyei-
cosatrienoic acid. Hydroxyepoxyeicosatrienoic and trihydroxyeicosatrienoic acids
are endothelium-derived hyperpolarizing factors that activate calcium-activated,
small-conductance K Ca 2 channels [ 825 ]. In vascular endothelium of other arter-
ies, arachidonate 12-lipoxygenase (ALOx12) produces 12-hydroxyeicosatetraenoic
acid that relaxes smooth myocytes via calcium-activated, large-conductance K Ca 1
channel [ 825 ].

ω

Adrenomedullin

Adrenomedullin activates nitric oxide synthase. It then causes vasodilation and
possible hypotension. Adrenomedullin is a peptide similar to calcitonin gene-
related peptide (CGRP). Hence, it belongs to the calcitonin-CGRP-amylin peptide
family [ 826 ].
Adrenomedullin is manufactured from a precursor, the preproadrenomedullin.
The adrenomedullin gene is highly expressed in endothelial cells. It also functions
in many cell types, such as vascular smooth myocytes, cardiomyocytes, and blood
cells. Adrenomedullin circulates in blood (concentration: 2-4 pmol).
Adrenomedullin increases the cellular cAMP level via Gs activation. It modifies
the intracellular amount of calcium and cGMP messengers.