Table 1.

Summary of experimental studies demonstrating the beneficial effects of targeting reactive oxygen species (ROS), HIF-1 and the endothelin-1 (ET-1) system in animal models of cardiovascular complications associated with intermittent hypoxia (IH).

Gp91phox: MnTBAP: Mn(III)tetrakis(4-benzoic acid)porphyrin chloride; NOX2: gp91phox subunit of NADPH oxidase.

Cardiovascular disease	IH model	Target	Treatment/Models	References
Systemic hypertension	Rat	ROS	Melatonin (10 mg/kg/day)	(Hung et al., 2013)
	Rat	ROS	Tempol (1 mM in water)	(Ramond et al., 2013)
	Rat	ET-1	PD145065 (1–1000 nmol/kg)	(Kanagy et al., 2001)
	Rat	ET-1	BQ-123 (10–1000 nmol/kg)	(Allahdadi et al., 2008)
	Rat	ET-1	Bosentan (100 mg/kg/day)	(Belaidi et al., 2009)
	Mouse	ROS	Apocynin (30 mg/kg/day)/NOX-2 deficiency	(Schulz et al., 2014)
	Mouse	ET-1	Bosentan (30 mg/kg/day)/PD155080 (50μg/kg/day)	(de Frutos et al., 2010)
Vascular dysfunction	Rat	ROS	Allopurinol (65 mg/kg/day)	(Dopp et al., 2011)
	Rat	ROS	Atorvastatin (10 mg/kg/day)	(Totoson et al., 2013)
	Rat	ET-1	BQ-123 (10 μM perfusion)	(Mentek et al., 2016)
	Mouse	ROS	MnTBAP (100 μM perfusion)	(Capone et al., 2012)
	Mouse	ET-1	BQ-123 (10 μM perfusion)	(Capone et al., 2012)
Vascular remodeling	Mouse	ET-1	Bosentan (30 mg/kg/day)/PD155080 (50μg/kg/day)	(de Frutos et al., 2010)
	Mouse	ET-1	Bosentan (100 mg/kg/day)	(Gras et al., 2016)
	Mouse	HIF-1	HIF-1 deficiency	(Gras et al., 2016)
Cardiac dysfunction	Rat	ROS	Allopurinol (1% in water)	(Williams et al., 2010)
Cardiac remodeling	Mouse	ROS	NOX2 deficiency	(Hayashi et al., 2008)
Myocardial infarction	Rat	ROS	Melatonin (100 mg/L)/Tempol (1 mM in water)	(Ramond et al., 2013)
	Rat	ET-1	Bosentan (100 mg/kg/day)	(Belaidi et al., 2009)
	Mouse	HIF-1	HIF-1 deficiency	(Belaidi et al., 2016)
Stroke	Mouse	ROS	MnTBAP (100 μM perfusion)/NOX2 deficiency	(Capone et al., 2012)
	Mouse	ET-1	BQ-123 (10 μM perfusion)	(Capone et al., 2012)