Table 4.
Studies evaluating the effects of AHDs on BP in animal models of CIH.
| Species | CIH experimental protocol | Drugs/ intervention | BP measurement | Drug effect on BP | References |
|---|---|---|---|---|---|
| Sprague-Dawley rats | 2/3–20.9% O2 (3–6 s + 15–18 s; 2 cycles/min); 6–8 h/day; 35 days | Losartan (15 mg/kg); gavage; 35 days | Telemetry | Significant ↓ MAP (98.2 ± 61.7 to 85.9 ± 62.7 mm Hg) | Fletcher et al., 1999 |
| Sprague-Dawley rats | 5–21% O2+ 5–0%CO2 (20 cycles/h); 7 h/day; 14 days | A-779 (Ang-(1–7) antagonist); Losartan (2 nmol/h) and ZD7155 (AT1 antagonists); PD123319 (AT2 receptor antagonist); osmotic minipumps delivered into PVN; 14 days. | Telemetry | ↓ MAP: A-779: 5 ± 1 mm Hg, Losartan: 9 ± 4 mmHg, ZD7155: 11 ± 4 mmHg PD123319: 4 ± 3 mmHg | da Silva et al., 2011 |
| Sprague-Dawley rats | 20.9–10% (180 s cycles); 10 h/day; 35 days | Losartan (15 mg/kg); p.o. (syringe technique); 35 days | NA (arterial catheterization?) | ↓ SBP (10 mmHg) | Fenik et al., 2012 |
| Sprague-Dawley rats | 80 cycles (6 min each) 21–10% O2/day; 8 h/day; 7 days | Losartan (1 μg/h); intracerebroventricular (miniosmotic pumps); 7 days | Telemetry | ↓ MAP during both CIH exposure and normoxic period | Knight et al., 2013 |
| Sprague-Dawley rats | 20 cycles (90 s each) of 21–5% O2 and 0–5% CO2/h; 7 h/day; 14 days | BQ-123 (10–1000 nmol/kg in bolus or 100 nmol/kg/day for chronic administration); iv or sc; 14 days | Tail-cuff method and telemetry | Acute administration: dose dependent ↓ MAP Chronic administration: prevented ↑MAP | Allahdadi et al., 2008 |
| SHR + Wistar rats | 21–10% O2 (1 min cycles: 20 + 40 s); 8 h/day; 14 days | Bosentan (100 mg/Kg/dia); mixed in chow; 14 days | Tail-cuff method + Arterial catheterization | Prevented ↑MAP | Belaidi et al., 2009 |
| SHR | 21–10% O2 (every 90 s); 12 h/day; 30 days | Nifedipine (5 mg/Kg) and SOD mimetic (MnTMPyP; 10 mg/Kg); s.c.; 30 days | Tail-cuff method | Nifedipine: attenuate SBP and DBP SOD mimetic: ↓ SBP and DBP | Soukhova-O'Hare et al., 2008 |
| Sprague-Dawley rats | 21–5% O2 (every 60 s); 8 h/day; 14–21 days | Melatonin (10 mg/Kg); i.p.; 14 or 21 days (30 min before hypoxic exposure) | Tail-cuff method | ↓ SBP (21 mmHg) | Hung et al., 2013 |
| Sprague-Dawley rats | 20 cycles (90 s each) of 21–5% O2 and 0–5% CO2/h; 7 h/day; 14 days; | Tempol (1 mM); drinking water; 14 days | Telemetry | ↓ MAP (17 mmHg) | Troncoso Brindeiro et al., 2007 |
| Sprague-Dawley rats | 12 cycles (300 s each) of 21–5% O2/h; 8 h/day; 21 days | Ascorbic acid (1.25 g/L); drinking tap water; 21 days | Arterial catheterization | ↓ MAP (29 mmHg) | Del Rio et al., 2010 |
| Sprague-Dawley rats | 9 cycles (5 min + 15 s) of 21–5% O2/h; 8 h/day; 10 days | SOD mimetic (MnTMPyP; 5 mg/Kg/day); i.p; 10 days | Arterial catheterization | ↓↓ MAP | Kumar et al., 2006 |
| Sprague-Dawley rats | 20 cycles (90 s each) of 21–5% O2 and 0–5% CO2/h; 8 h/day; 11 days | PD145065 (ET receptor antagonist in cumulative drugs: 0.3, 3.0, 30, 300, 1000 nmol/Kg); bolus; 11 days | Arterial catheterization | Dose dependent ↓ MAP | Kanagy et al., 2001 |
| Sprague-Dawley rats | 21–5% O2 (12 times/h); 8 h/day; 14 days | Ebselen (specific ONOO- scavenger; 10 mg/kg/day); osmotic mini-pumps; 7 days | Telemetry | ↓ elevated BP | Moya et al., 2014 |
AHDs, antihypertensive drugs; BP, blood pressure; CIH, chronic intermittent hypoxia; DBP, diastolic blood pressure; ET, endothelin; h, hour; HT, hypertension; i.p., intraperitoneal; MAP, mean arterial pressure; NA, information not available; min, minutes; p.o., per os; PVN, hypothalamic paraventricular nucleus; s, seconds; SBP, systolic blood pressure; SHR, spontaneously hypertensive rats; s.c., subcutaneous; SOD, superoxide dismutase mimetic; ↓, decrease; ↑, increase.