Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 587

To match perfusion to ventilation, the pulmonary circulation responds differently
to numerous stimuli, such as ROS and hypoxia. In response to hypoxia, pulmonary
and systemic arteries generally constrict and dilate, respectively [ 1143 ]. In chronic
obstructive pulmonary diseases, ROS can cause pulmonary hypertension.
In pulmonary arteries, superoxide anion causes RoCK-dependent Ca 2 + sensiti-
zation; in systemic (mesenteric) and pulmonary arteries, superoxide anion provokes
opening of voltage-gated K + channel, but only primes dilation in mesenteric
arteries [ 1143 ]. Superoxide also relaxes preconstricted coronary and renal arteries.
Vasoconstriction depends mainly on non-selective cation channels in pulmonary
arteries, principally on voltage-gated Ca 2 + channels in mesenteric arteries.
Reactive oxygen species are involved in the regulation of cerebral vascular
tone [ 1144 ]. According to the context, ROS can either generate or prevent calcium
sparks, i.e., can contract or relax vascular smooth myocytes. Moreover, ROS can
interact with other substances, such as nitric oxide and arachidonic acid, thereby
changing vascular tone.
Cerebral vasodilation results from action of products of univalent reduction of
oxygen — superoxide anion radical, hydroxyl radical, and hydrogen peroxide —
as well as peroxynitrite on cerebral arterioles [ 1145 ]. Application of hydrogen
peroxide and peroxynitrite in anesthetized cats equipped with cranial windows
induces dose-dependent dilation of cerebral arterioles via ATP-sensitive potassium
channels. On the other hand, superoxide causes a dose-dependent dilation of cere-
bral arterioles via calcium-activated potassium channels. Although peroxynitrite
can dilate cerebral arteries by activating potassium channels, it also may impair
responses mediated by the same or other types of K + channels. Peroxynitrite may
be responsible for impaired vasodilation during hypoxia-reoxygenation in response
to the endothelium-dependent messenger acetylcholine [ 1146 ].
In cerebral arteries, superoxide causes vasodilation via potassium channels and
vasoconstriction at low and high concentrations, respectively [ 1144 ]. Superoxide
may act directly on smooth myocytes of cerebral arteries and indirectly via
endothelium. It interacts rapidly with nitric oxide, hence governing nitric oxide half-
life and attenuating NO-mediated vasodilation. Furthermore, peroxynitrite produced
by the reaction of nitric oxide with superoxide influences vascular tone.
Exogenous hydrogen peroxide relaxes small cerebral arteries and arterioles via
potassium channels [ 1144 ]. Very high H 2 O 2 concentrations can provoke vasocon-
striction followed by vasodilation. This relaxing factor may act as an endothelium-
derived hyperpolarizing factor or not according to the arterial compartment.
Arachidonic acid and bradykinin produce dilation of cerebral arterioles via
endothelium and reactive oxygen species, more precisely hydrogen peroxide [ 1144 ].
Bradykinin binds to B 2 receptor and activates cyclooxygenase-1 that processes
arachidonic acid and produces superoxide. On the other hand, vasodilation of
cerebral vessels caused by acetylcholine and ATP is not influenced by reactive
oxygen species.