Salt and Nitric Oxide Inhibition Induced Hypertension: The Role of Prostacycline and 8-Isoprostane
Firat University, Faculty of Medicine, Department of Pharmacology, Elaziğ, Turkey.Clinical and Experimental Hypertension (Impact Factor: 1.23). 04/2011; 33(2):84-8. DOI: 10.3109/10641963.2010.503305
Renal prostacycline (PGI(2)) and oxidative stress are known to be important factors that effect the natriurezis and diuresis. 8-iso prostaglandin F(2)α± (8-isoprostane), a member of F(2)-isoprostanes, is formed from the nonenzymatic reaction of arachidonic acid and oxygen radicals in vivo and in vitro, and also it is a marker of oxidative stress in vivo. The aim of this study is to determine the role of renal PGI(2) and 8-isoprostane in a salt and nitric oxide (NO) inhibition-induced hypertension model. Rats were distributed equally among four groups (n = 6 per group). Control rats were given normal salt diet (0.32%); high-salt (HS) rats were given high salt diet (3.2%); NG-nitro-L-arginine (L-NNA) rats were given normal salt diet and 25 mg/kg L-NNA; HS+L-NNA rats were given high salt diet and 25 mg/kg L-NNA. Rats were placed in individual metabolic cages for 17 days. Systolic blood pressure (SBP) was measured at days initial, 7th and 14th .Urinary 8-isoprostane and PGI(2) levels were analyzed. Salt- loading alone did not change SBP values. The average SBP in L-NNA and HS+L-NNA groups were shown to significantly enhance compared to initial and day 7th in the same groups, respectively. The levels of 8-isoprostane in the HS+L-NNA group was significantly enhanced compared to the other groups. L-NNA or HS diet alone did not change the levels of 8-isoprostane compared to the control group. L-NNA alone did not change PGI(2) levels in urine compared to the control. PGI(2) levels in the HS, and the HS+L-NNA group was significantly higher compared to the control group. This study concluded that NOS inhibition plus salt-loading induced oxidative stress and increased renal PGI(2). Also, it is suggested that augmented oxidative stress may aggravate the hypertension. But the renal synthesis of PGI(2) is increased in order to augment the diuresis and natriuresis without the effect of blood pressure (BP).
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ABSTRACT: Hypertension is a common disease and a potent risk factor for cardiovascular disease. Tremendous strides have been made in understanding its genesis in the last 2 decades. Hypertension is often clustered with other cardiovascular risk factors, such as dyslipidemia and diabetes. The state of hypertension is often associated with increased vascular oxidative stress. Oxidative stress promotes proliferation and hypertrophy of vascular smooth muscle cell and collagen deposition, leading to thickening of the vascular media and narrowing of the vascular lumen. Oxidative stress also injures endothelium, impairs endothelium-dependent vascular relaxation and increases vascular contractile activity. Further, oxidative stress also oxidizes LDL-cholesterol. It has been shown that oxidized low-density lipoprotein (ox-LDL) activates renin-angiotensin system (RAS) and angiotensin II via its type 1 receptor activates ox-LDL receptor LOX-1. This mutually facilitative cross-talk between ox-LDL and RAS may be an important component in the development of hypertension. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a receptor for ox-LDL. This review summarizes the role of LOX-1 in the pathogenesis of hypertension.
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ABSTRACT: Oxidative stress is believed to play a crucial role in aging and age-related diseases, and is widely thought to increase morbidity and mortality in the elderly. Assessment of biomarkers of oxidative stress, such as 8-isoprostane and 8-hydroxy-2-deoxyguanosine, are considered to be useful in predicting disease risks at the population level. The aim of the present study was to assess the health status of the elderly by comparing their lifestyles and levels of oxidative stress biomarkers. We carried out a cross-sectional study where urine samples from a total of 100 elderly men and women were assayed for 8-isoprostane, 8-hydroxy-2-deoxyguanosine, selenium, cadmium and creatinine. They were asked to answer a questionnaire that included questions about their lifestyle. Most of the participants were prehypertensive, non-alcohol users and on a rich plant-based diet. There were no differences in any biomarkers of oxidative stress between men and women. 8-Isoprostane was found to correlate positively with systolic blood pressure in women, but not in men. There was a slight increase of 8-isoprostane in participants with a poor intake of vegetables, and a decrease of 8-hydroxy-2-deoxyguanosine in participants who consumed fish. Multiple regression analysis showed that oxidative stress biomarkers were positively associated with cadmium, and negatively associated with selenium and fish intake in all participants, 89% of which were non-smokers. Results from the present study show that fish intake has the potential of decreasing oxidative stress among elderly persons.
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ABSTRACT: Objective: The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a polychlorinated dibenzo-para-dioxin. Methods: A total of 24 Sprague-Dawley rats were divided equally into the following four groups: (1) control group was administered with 0.5 mL corn oil by gavage and 0.5 cc vehicle of melatonin (proportionally nine parts physiological serum + one part ethyl alcohol) intraperitoneally for 4 weeks, (2) the melatonin group was given 5 mg/kg/day melatonin intraperitoneally for 4 weeks, (3) the TCDD group was given 500 ng/kg/day TCDD by gavage for 4 weeks and (4) the TCDD + melatonin group was given TCDD (500 ng/kg/day) by gavage and melatonin (5 mg/kg/day) intraperitoneally simultaneously for 4 weeks. Systolic blood pressure was evaluated by the tail-cuff method. Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas. Results: TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta. Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta. TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it. Therefore, TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it. Conclusion: Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity. However, melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD.
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