Benefit of azilsartan on blood pressure elevation around rest-to-active phase in spontaneously hypertensive rats.

Abnormal elevation of blood pressure in early morning (rest-to-active phase) is suggested to cause cardiovascular events. We investigated whether azilsartan (AZL), a novel potent angiotensin receptor blocker, suppresses blood pressure elevation from the light-rest to dark-active phase in spontaneously hypertensive rats (SHRs). AZL has a sustained depressor effect around the rest-to-active phase in SHRs to a greater extent than candesartan (CAN), despite their similar depressor effects for over 24 h. AZL did not cause sympathoexcitation. These results suggest that AZL has a more sustained depressor effect than CAN around the rest-to-active phase in SHRs, and might have advantages for early morning hypertension.

Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

Angiotensin II type 1 receptor expression in astrocytes is upregulated leading to increased mortality in mice with myocardial infarction-induced heart failure.

Enhanced central sympathetic outflow worsens left ventricular (LV) remodeling and prognosis in heart failure after myocardial infarction (MI). Previous studies suggested that activation of brain angiotensin II type 1 receptors (AT1R) in the brain stem leads to sympathoexcitation due to neuronal AT1R upregulation. Recent studies, however, revealed the importance of astrocytes for modulating neuronal activity, but whether changes in astrocytes influence central sympathetic outflow in heart failure is unknown. In the normal state, AT1R are only weakly expressed in astrocytes. We hypothesized that AT1R in astrocytes are upregulated in heart failure and modulate the activity of adjacent neurons, leading to enhanced sympathetic outflow. In the present study, by targeting deletion of astrocyte-specific AT1R, we investigated whether AT1R in astrocytes have a key role in enhancing central sympathetic outflow, and thereby influencing LV remodeling process and the prognosis of MI-induced heart failure. Using the Cre-LoxP system, we generated glial fibrillary acidic protein (GFAP)-specific AT1R knockout (GFAP/AT1RKO) mice. Urinary norepinephrine excretion for 24 h, as an indicator of sympathoexcitation, was significantly lower in GFAP/AT1RKO-MI mice than in control-MI mice. LV size and heart weight after MI were significantly smaller in GFAP/AT1RKO mice than in control mice. Prognosis was significantly improved in GFAP/AT1RKO-MI mice compared with control-MI mice. Our findings indicated that AT1R expression was upregulated in brain stem astrocytes in MI-induced heart failure, which worsened LV remodeling and prognosis via sympathoexcitation. Thus, in addition to neuronal AT1R, AT1R in astrocytes appear to have a key role in enhancing central sympathetic outflow in heart failure.

Exercise training causes sympathoinhibition through antioxidant effect in the rostral ventrolateral medulla of hypertensive rats.

Exercise training normalizes sympathetic outflow in hypertension and chronic heart failure. The aim of this study was to determine whether the exercise training inhibits sympathetic nerve activity (SNA) via reduction of oxidative stress through blocked angiotensin II type 1 receptor (AT(1)R) in rostral ventrolateral medulla (RVLM). We divided stroke-prone spontaneously hypertensive rats (SHRSP) into SHRSP with exercised training (SHRSP-EX) and control (SHRSP-C). SNA and oxidative stress in the RVLM were significantly lower in SHRSP-EX than in SHRSP-C. These results suggest that exercise training inhibits SNA via reduction of oxidative stress through blocked AT(1)R in the RVLM of hypertension.

A case of coronary subclavian vertebral steal syndrome successfully treated with stenting to the stenosis of left subclavian artery.

Coronary subclavian vertebral steal syndrome (CSVSS) is a rare but important complication of coronary artery bypass graft surgery (CABG) when an internal mammary artery (IMA) is used. This syndrome is defined as a retrograde flow from coronary artery via the IMA and the vertebral artery to the subclavian artery due to a proximal subclavian artery stenosis. We describe a case of a 64-year-old female who underwent CABG, complaining of dyspnea and chest pain by exercise of left arm, and dizziness when she turned her face to the left. Her blood pressure was 113/69 mmHg in the left arm and 137/84 mmHg in the right arm. Coronary angiography revealed retrograde flow from the left anterior descending (LAD) artery to the left IMA. Aortography showed that the ostium of the left subclavian artery had a severe stenosis and that the left vertebral artery was visualized retrogradely. Thereby, the diagnosis of CSVSS was made. The stenosis of the left subclavian artery was successfully treated with a percutaneous transluminal angioplasty and stent implantation, resulting in the restoration of antegrade flow from the left IMA to the LAD artery and from the left subclavian artery to the left vertebral artery. She was discharged with no chest pain and dizziness. .