Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 441

Table 8.27. Isozymes of NADPH oxidase (NOx) and reactive oxygen species in the pulmonary
vasculature: their functions and lung diseases (Source: [ 816 ]; DuOx: dual oxidase; EC: endothelial
cell; MFb: myofibroblast; REpC: respiratory epithelial cell; SMC: smooth myocyte; ARDS: acute
respiratory distress syndrome; CGD: chronic granulomatous disease; COLD: chronic obstructive
lung disease; PAH; pulmonary arterial hypertension). Isozyme NOx4 is highly expressed in
endothelial and pulmonary artery smooth muscle cells.

Subtype Location Function Lung disease

NOx2/4 Arterial EC Control of vascular tone, ARDS

remodeling, angiogenesis, PAH

inflammatory cytokine production

NOx2 Macrophages, CGD

neutrophils

NOx3 EC Emphysema

NOx4 Arterial SMC Cell differentiation, PAH

hypoxia-induced proliferation

MFb Cell differentiation, Fibrosis

DuOx1/2 REpC Host defense, mucin production, COLD,

cell migration and differentiation asthma

Lung carcinoma cell Cancer

Hypoxia increases ROS signaling in pulmonary arterial smooth muscle
cells [ 816 ]. Hypoxia upregulates NOx4 expression via hypoxia-inducible factor-1 .

Hypoxia-induced ROS may inhibit K V 1.5 and K V 2.1 channels (mainly), thereby
causing membrane depolarization and subsequently activating Ca V 1.2 channels.
In addition, hypoxia causes activation of protein kinase-C

α

. Hydrogen peroxide

provokes constriction of pulmonary arteries via PKC . In fact, several PKC

isoforms are involved in hypoxic pulmonary vasoconstriction. In particular, PKC

α

ζ
contributes to NOx activation. On the other hand, superoxide triggers the RoCK
pathway, hence constriction of pulmonary arteries [ 816 ]. In addition, ROS stimulate
cyclooxygenases.

8.5.8.5 Vasodilators

The 3 main endothelial processes that generate vascular smooth muscle relaxation—
nitric oxide, prostacyclin (PGi2), and endothelial-derived hyperpolarizing factor
(EDHF) — involve fatty acid cycling. Endothelial nitric oxide synthase is reversibly
palmitoylated. Palmitoylation allows NOS3 cycling between the plasma membrane,
where NOS3 is inactive, and the cytosol, where it is active.

β -Adrenoceptors

Vascular smooth myocytes synthesize multiple adenylate cyclase subtypes; AC3,
AC5, and AC6 have the highest expression. Adenylate cyclase isozymes are