The action of taxifolin on the angiotensinconverting enzyme (ACE) and the formation of reactive oxygen and nitrogen species (ROS/RNS) in the aorta of aging rats and rats treated with nitric oxide synthase inhibitor (N ω -nitro-L-arginine methyl ester (L-NAME)) or dexamethasone have been studied. The ACE activity in aorta sections was determined by measuring the hydrolysis of hippuryl-L-histidyl-L-leucine, and the ROS/ RNS production was measured by oxidation of dichlorodihydrofluorescein. It was shown that taxifolin at a dose of 30-100 μg/kg/day decreases the ACE activity in the aorta of aging rats and of rats treated with L-NAME or dexamethasone to the level of the ACE activity in young control rats. Taxifolin (100 μg/kg/day) was found to also reduce the amount of ROS/RNS in the aorta that increased as a result of L-NAME intake. L-NAME treatment increases the contribution of 5-lipoxygenase and NADPH oxidase to ROS/RNS production in the aorta, while taxifolin (100 μg/kg/day) decreases the contribution of these enzymes to the normal level.
We studied changes in ROS content in the aorta of Wistar rats at early terms after irradiation in doses equal to single fraction used in tumor radiotherapy and the effects of taxifolin and fucoidin, blockers of leukocyte adhesion to endothelium, on ROS content. Male rats were exposed to X-rays (200 kW) in doses of 1-7.5 Gy. ROS production in aorta segments was measured in 1-48 h after irradiation by dichlorodihydrofluorescein oxidation. The content of ROS in the aorta of rats exposed to radiation in doses of 1-2.5 Gy increased in 1-24 h after irradiation, the peak ROS content was found in 2 h after irradiation. Taxifolin (100 μg/kg dihydroquercetin once a day with drinking water) and fucoidin (10 mg/kg, i.v.) abolished ROS accumulation. The content of ROS in rat aorta increased in 1-24 h after irradiation in doses used for tumor radiotherapy and this increase can be determined by leukocyte adhesion to the endothelium.
We analyzed changes in angiotensin-converting enzyme activity in the aorta of hypertensive SHR rats against the background of age-related BP increase (from week 7 to 14) and the effect of dihydroquercetin on BP rise and angiotensin-converting enzyme activity. Normotensive WKY rats of the same age were used as the control. BP and activity of angiotensin-converting enzyme in the aorta of SHR rats increased with age. Dihydroquercetin in doses of 100 and 300 μg/kg per day had no effect on the increase of these parameters; dihydroquercetin administered to 14-week-old WKY rats in a dose of 300 μg/kg reduced activity of the angiotensin-converting enzyme. Thus, the early (7-14 weeks) increase in BP and angiotensin-converting enzyme activity in the aorta of SHR rats was not modified by flavonoids (dihydroquercetin) in contrast to other rat strains and humans, which is indicative of specificity of hypertension mechanism in SHR rats.
We studied the effect of camel thorn extract on activity of angiotensin-converting enzyme in rat aorta increased in animals during aging or treatment with NO-synthase inhibitor. Intake of camel thorn extract with drinking water reduced activity of angiotensin-converting enzyme; the effect increased with increasing the dose of the extract. Angiotensin-converting enzyme activity in older rats and animals treated with NO-synthase inhibitor decreased to the values observed in young control rats at extract concentration of 0.2%. Comparison of the effects of camel thorn extract with those of flavonoid taxifolin showed that the extract was not inferior to taxifolin in preventing the early stages of aortic atherosclerosis caused by increased activity of angiotensin-converting enzyme.
The dynamics of angiotensin-converting enzyme activity in the aorta and blood plasma and generation of ROS in the aorta were studied in rats subjected to two high-salt diets (0.4% and 1% NaCl solutions). During high-salt diets, activity of angiotensin-converting enzyme in the aorta progressively decreased to the minimal during week 1 and remained lower than control level for 1 month. Both diets were followed by a decrease in ROS concentration in the aorta, and this effect was more pronounced when the dosage of salt increased. ROS level in the aorta varied similarly during both diets, but the amplitude of the response was significantly higher in rats receiving 0.4% salt solution. ROS amount in the aorta during high-salt diets differed from the control level and depended from salt dosage and the duration of administration.
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