Pulmonary Hypertension Is a Probable NO/ONOO⁻ Cycle Disease: A Review

Table 1

NO/ONOO⁻ cycle elements implicated in PAH initiation.

Initiator	NO/ONOO^− cycle element.
High altitude/hypoxia	Increased intracellular calcium, TRP receptor activity elevation, iNOS induction, (BH4 depletion?)
Viral infection	NF-𝜅B elevation, elevated inflamm. cytokines, iNOS induction, NO elevation, ONOO^− elevation, oxidative stress
Ritonavir	Oxidative stress, superoxide elevation, mitochondrial dysfunction
Tuberculosis	NF-𝜅B elevation, elevated inflamm. cytokines, iNOS induction, NO elevation, ONOO^− elevation
Endotoxin	NF-𝜅B elevation, elevated inflamm. cytokines, iNOS induction, NO elevation, ONOO^− elevation, oxidative stress, (NMDA elevation?)
Homocysteine	NMDA elevation, superoxide elevation
Paraquat	Mitochondrial dysfunction, elevated NMDA activity, oxidative stress, elevated inflamm. cytokines, NF-𝜅B elevation
Systemic autoimmune disease	Oxidative stress, inflamm. cytokine elevation; ONOO^− elevation, superoxide elevation, inflamm. cytokine elevation, BH4 depletion, elevated intracellular calcium, NF-𝜅B elevation
BPMR2 mutation	Superoxide, oxidative stress, mitochondrial dysfunction
Serotonin	Oxidative stress, inflamm. cytokine elevation, ONOO^− elevation, superoxide elevation, inflamm. cytokine elevation, NF-𝜅B elevation
Bleomycin	PARP elevation, oxidative stress, superoxide elevation, inflamm. cytokine elevation, BH4 depletion, mitochondrial dysfunction, NF-𝜅B elevation
VIP deficiency	BH4 deficiency, inflammatory cytokine elevation
BH4 deficiency	BH4 deficiency, superoxide elevation