Abstract
Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P < 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P < 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P < 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.
Highlights
Hypertension is a common cardiovascular disease and the main risk factor for malignant cardiovascular events, such as coronary heart disease and stroke
Arterial blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), increased significantly in spontaneously hypertensive rats (SHR)-CON rats compared with WKY control group (WKY-CON) rats (P < 0.05– 0.01), but decreased significantly in SHR-chronic intermittent hypobaric hypoxia (CIHH) rats compared with SHR control group (SHR-CON) rats (P < 0.01)
The decreasing effect of CIHH on SBP and DBP in SHR lasted 3–4 weeks (Figure 2). These results indicate that CIHH had an effective anti-hypertensive effect but no effect on heart rate (HR) in hypertensive rats
Summary
Hypertension is a common cardiovascular disease and the main risk factor for malignant cardiovascular events, such as coronary heart disease and stroke. Numerous studies have demonstrated the beneficial effects of chronic intermittent hypobaric hypoxia (CIHH) on the heart, brain, liver, and kidneys under ischemia/reperfusion (I/R) or pathological conditions (Zhang and Zhou, 2012; Yuan et al, 2015; Tian et al, 2016; Zhang et al, 2016). Our previous studies showed that CIHH protects the heart against I/R injury, promotes the recovery of cardiac function, reduces the myocardial infarct area, and antagonizes arrhythmias in the I/R heart (Zhang et al, 2000; Zhou et al, 2013). CIHH effectively reduces arterial blood pressure in renovascular hypertensive rats, which may be related to the facilitation of the baroreflex and enhanced vascular relaxation (Guan et al, 2016; Li et al, 2016). Previous studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH
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