Endothelin‐1 (ET‐1) is a 21 amino acid vasoconstrictor and implicated in the regulation of hypertention. Recently, our colleagues found that transgenic mice (TET‐1) with endothelial ET‐1 over‐expression developed hypertention in young mice by changing vascular properties. However, the effects of over‐expressing endothelial ET‐1 on cardiovascular system in aged mice are still unclear. Therefore, this study investigated the blood pressure and heart rate of TET‐1 aged mice and non‐transgenic (NTg) aged mice (1.5‐2 years old). A non‐invasive tail cuff measurement showed that a significant elevation of both systolic (115.1 ± 2.935 vs 103.5 ± 1.846 mmHg, p <0.01) and diastolic (85.81 ± 2.303 vs 74.56 ± 2.029 mmHg, p <0.05) in conscious TET‐1 aged mice comparing to NTg counterpart, indicating over‐expressed endothelial ET‐1 cause both systolic and diastolic hypertension in aged mice. And, aged TET‐1 mice showed a significantly decreased heart rate to aged NTg mice (616.7 ± 20.14 vs 670.9 ± 11.57 beats per minute (bpm), p <0.05). Moreover, Rate‐pressure product is a sensitive index of myocardial oxygen consumption, and it was not altered in TET‐1 mice (71085 ± 3258 vs 69337 ± 1233 bpm*mmHg, p >0.05), implicating over‐expressed endothelial ET‐1 would change cardiovascular properties by mechanisms of mutual compensation between blood pressure and heart rate. These findings provide evidence for roles of endothelial ET‐1 in altering cardiovascular system in aged mice. This study also implicates clinical importance of endothelial ET‐1 as a therapeutic target for hypertension in the elderly. Grant Funding Source : Supported by the departmental fund, Department of Anaesthesiology, The University of Hong Kong
Under pathological conditions in the adult CNS, such as ischemia, subarachnoid hemorrhage and Alzheimer's disease, endothelin (ET)-1- and -3-like immunoreactivities are elevated in astrocytes of the injured adult brain. However, it is not clear whether this is due to increased synthesis or increased binding of ET-1. Further, it is not known whether ET-1 expression is altered in the perinatal brain after cerebral hypoxia/ischemia (H/I). Here, we determined the sites of ET-1 expression in perinatal mouse brain after H/I injury by in situ hybridization using a probe specific for the ET-1 gene. Astrocyte-like cells, which do not normally express ET-1 mRNA, showed high levels of ET-1 mRNA expression. Endothelial cells of the capillaries and small vessels also showed an increased level of ET-1 mRNA. Our data suggest that ET-1 mRNA levels in the astrocyte-like cells and vascular endothelial cells are dynamically regulated by ischemia and may participate in perinatal ischemia-related neural damage.
Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aβ and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy.
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