ACE2 gene combined with exercise training attenuates central AngII/AT1 axis function and oxidative stress in a prehypertensive rat model.

Angiotensin-converting enzyme 2 (ACE2) or exercise training (ExT) is beneficial to hypertension, but their combined effects remain unknown. In this study, lentivirus containing enhanced green fluorescent protein (eGFP) and ACE2 were microinjected into the paraventricular nucleus (PVN) of young male spontaneous hypertensive rats (SHRs), and SHRs were assigned into five groups: sedentary (SHR), SHR-ExT, SHR-eGFP, ACE2 gene (SHR-ACE2), and ACE2 gene combined with ExT (SHR-ACE2-ExT). Wistar-Kyoto (WKY) rats were used as a control. ACE2 gene or ExT significantly delayed the elevation of blood pressure, and the combined effect prevented the development and progression of prehypertension. Either ACE2 overexpression or ExT improved arterial baroreflex sensitivity (BRS), whereas the combined effect normalized BRS in SHR. Compared with SHR, SHR-ACE2 and SHR-ExT displayed a significantly higher level of ACE2 protein but had lower plasma norepinephrine (NE) and angiotensin II (AngII) as well as angiotensin II type 1 receptor (AT1) protein expression in the PVN. SHR-ACE2-ExT showed the largest decrease in AngII and AT1 protein expression. Reactive oxygen species (ROS) level and NADPH oxidase (NOX2 and NOX4) protein expression in PVN were also decreased in SHR-ACE2-ExT group than in SHR-ACE2 and SHR-ExT groups. It was concluded that the combined effect has effectively prevented prehypertension progression and baroreflex dysfunction in SHR, which is associated with the reduction in AngII/AT1 axis function and oxidative stress in the PVN.NEW & NOTEWORTHY Angiotensin-converting enzyme 2 (ACE2) gene in combination with exercise training (ExT) delayed the progression of hypertension via normalizing the blunted baroreflex sensitivity (BRS) and inhibiting sympathetic nerve activity (SNA). Its underlying mechanism may be related to the inhibition of AngII/AT1 axis function and central oxidative stress in the paraventricular nucleus (PVN) of prehypertensive rats.

[Study of intracerebral focus changes on CADASIL by using MR imaging].

OBJECTIVE: To investigate dynamic changes of intracerebral focus on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: Using the modified Scheltens scale, the magnetic resonance (MR) changes of lesion distribution, size and shape in 7 patients from a CADASIL family were retrospectively analyzed during 3 years observed. RESULTS: In 6 of 7 patients, the number and volume of lesion areas in the white matter were increased (parietal lobe, n = 6; temporal lobe, n = 5; frontal lobe, n = 3; occipital lobe, n = 2) and some areas even became confluent as a mass or chain. New lacunar infarcts (n = 1 - 5) appeared in 5 patients and the arcuate fiber were involved in 1 patients. Slight enlargement could be seen in lateral ventricle (n = 1) or lateral ventricle with third ventricle (n = 1). CONCLUSION: MR imaging can help us to reveal dynamic changes of brain lesions and prognosis in patients with CADASIL.

[Use W303-1A/hER-ERE-Lac Z to determine estrogenic compounds in traditional Chinese materia medica].

OBJECTIVE: To study the content of phytoestrogen in dissimilarity herbs. METHOD: The activity of phytoestrogen in heat-clearing drugs, drugs for relieving exterior syndrome, diuretic, anastaltics, tonics and astringents were detected based on the recombinant yeast cell (W303-1A/hER-ERE-Lac Z). The estrogenic activity in traditional Chinese materia medica were assayed quantitatively by determining the expression of beta-galactosidase. RESULT: The phytoestrogen concentration (6.35 x 10(-3) nmol x g(-1) E2 equivalent) in heat-clearing drugs was the highest while that in anastaltic and tonic drugs was the lowest, which was less than the detected limit. CONCLUSION: Compared with the other traditional Chinese materia medica, the content of phytoestrogen, which can bind to estrogen receptor, in giant knotweed rhizome, forsythia suspense, ash bark, baical skullcap root and ophiopogonis tuber were higher.

[The cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

OBJECTIVE: To investigate the cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: The blood flow velocity of cerebral arteries was measured by using transcranial Doppler ultrasound (TCD) in 6 cases with CADASIL and a quite number of age and sex matched control subjects. All patients (4 were symptomatic and 2 asymptomatic), being an established CADASIL family with the diagnosis confirmed by clinical characteristics, neuroimaging, pathology and molecular genetics, had abnormal mark signals on MR imagining and no history of hypertension, diabetes, heart disease and migraine. A routinely TCD detection, including peak-systolic velocity (Vp), end-diastolic velocity (Vd), mean velocity (Vm) and pulsatility index (PI), was carried out on the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA) and vertebral arteries (VA) as well as the basilar artery (BA). A comparison between the cases and controls was made. Then, the changes of flow velocity in middle cerebral arteries (MCA) of the patients with CADASIL were observed before and after breathholding tests. In addition, brain CT perfusion imaging (CTP) was carried out in all the cases by using 16-slice spiral CT. RESULTS: The appearances of frequency spectrum were nearly normal in all the cases and there was no abnormality between the two sides on velocity (P > 0.05). As compared with the controls, the bilateral Vp, Vd and Vm in ACA and PCA were decreased obviously (P < 0.05). The velocity parameters of MCA with the exception of left Vm and right PI showed changes (P < 0.05) and there were no changes of PI in the bilateral ACA, PCA and Left MCA (P > 0.05). Moreover, there were marked changes in MCA (including Vm, Vd and PI) of all the cases as compared with the controls after breathholding (P < 0.01). Brain perfusion imaging showing the regional cerebral blood flow and regional cerebral blood volume in frontal lobes were obviously decreasing (P < 0.01) and there was no significant variation of mean transit time (MTT). CONCLUSIONS: The characteristic hemodynamic changes in our group is the decreasing flow velocity in bilateral ACA, PCA and MCA and the dominating low flow area occurring usually in frontal and temporal lobes. These changes are in conformity with the ischemic area shown in pathology and neuroimaging in CADASIL patients.

[A study of subcortical infarcts and leukoencephalopathy (CADASIL) in a family with autosomal cerebral dominant arteriopathy].

OBJECTIVE: To investigate the clinical features, hereditary pattern, neuroimaging characteristics and diagnostic method of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: A systematic study on the clinical manifestations, neuroimaging characteristics, pathology and molecular genetics was performed. An investigation on the onset and hereditary pattern of the family tree of the proband was also done. RESULTS: The main clinical features of the proband including history of recurrent ischemic stroke, poor memory/cognition or dementia were noted. Fifteen cases pertaining to 4 generations of the proband with clinical or subclinical onset and confirmed classical family history of autosomal dominant hereditary were studied. Neuroimaging examination showed subcortical multiinfarct lesions and leukoencephalopathy. Electron microscope examination of the skin. Biopsy indicated thickening of basement membrane and presence of granular osmiophilic material (GOM) in the arterioles. A mutation on the fourth exon of notch 3 gene was revealed. Migraine, hypertension, diabetes and risk factors of arteriosclerosis were not found. All the features mentioned above in this family are in conformity with the diagnostic standard of CADASIL. CONCLUSIONS: It is possible to define CADASIL clinically by way of studying the clinical features, hereditary pattern, neuroimaging characteristics, skin biopsy and sequencing of gene without resorting to brain biopsy.