Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with marked neuroendocrinological dysfunction in addition to cardiac damage. The immediate trigger for AMI is not precisely known. Studies conducted by Lown, Braunwald, Halberg, Otsuka and our group have demonstrated a marked increase in sympathetic activity, oxidative stress, and magnesium and potassium deficiency during AMI. Clinical studies have reported an increased incidence of AMI, sudden death and ischemia during first quarter of the day when there is a rapid withdrawal of vagal activity and increase in sympathetic tone. In one case-control study of 202 patients with AMI, there was a significant (P < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter). This characteristic remained prevalent in both men and women and among patients with and without known AMI (n = 52), diabetes (n = 53) or hypertension (n = 75). Triggers of AMI were noted among 162 (82.2%) of the patients. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are are proinflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators of oxidative damage and proinflammatory activity, respectively.
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PMID:Mechanisms of acute myocardial infarction study (MAMIS). 1575 48

Preeclampsia (PE) is a multisystem disorder that remains a major cause of maternal and foetal morbidity and death. To date, no treatment has been found that prevents the development of the disease. Endothelial dysfunction is considered to underlie its clinical manifestations, such as maternal hypertension, proteinuria, and edema; however, the precise biochemical pathways involved remain unclear. A current hypothesis invokes the occurrence of oxidative stress as pathogenically important, as suggested by the fact that in PE, the placental and circulating levels of lipid peroxidation products (F2-isoprostanes and malondialdehyde [MDA]) are increased and endothelial cells are activated. A potential mechanism for endothelial dysfunction may occur via nuclear transcription factor kappa B (NF-kappaB) activation by oxidative stress. Alternatively, the idea that the antiangiogenic placental soluble fms-like tyrosine kinase 1 factor (sFlt1) is involved in the pathogenesis of this disease is just emerging; however, other pathophysiological events seem to precede its increased production. This review is focused on evidence providing a pathophysiological basis for the beneficial effect of early antioxidant therapy in the prevention of PE, mainly supported by the biological effects of vitamins C and E.
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PMID:Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins. 1589 47

Cyclosporine A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension and hepatotoxicity. Among possible mechanisms of CsA-induced hepatic damage, oxidative stress has been suggested. Melatonin (Mel) has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of some heat shock proteins (HSP) and the Mel antioxidant properties against CsA-induced injury. Rats were divided into four groups, which were treated respectively with olive oil, Mel alone, CsA and CsA plus Mel for 30 days. At the end of the treatments, the animals were killed and hepatic tissue was treated for morphological (haematoxylin-eosin), biochemical (reduced glutathione, GSH and malondialdehyde, MDA) and immunohistochemical (HSP60, HSP72, GRP75 and MT) analyses. The results indicate that CsA-induced hepatotoxicity was characterised by morphological alterations in tissue architecture, changes in GSH and MDA levels and increase in stress protein expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that Mel plays a protective action against CsA-induced oxidative stress, as supported by biochemical and immunohistochemical results.
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PMID:Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver. 1595 66

Losartan, an angiotensin II type-1 receptor (AT1) antagonist, was used to investigate whether it can offer protection against the sustained hypertension, cardiac hypertrophy, and renal damage induced by chronic inhibition of nitric oxide (NO) by Nomega-nitro-L-arginine methyl ester (L-NAME). We studied the involvement of both NO metabolism and oxidative stress in L-NAME-induced hypertension, and how AT1 receptor antagonism may interact. Male Wistar albino rats were subjected to NO synthesis inhibition by the use of L-NAME (60 mg/kg/day), and the effects of losartan (10 mg/kg/day) in drinking water for six weeks were observed. After six weeks, animals were subjected to the measurements for systolic, mean, and diastolic blood pressure (BPs, BPm, and BPd, respectively). Under light ether anesthesia blood was withdrawn for ACE activity, NOx and creatinine determinations. Heart and kidneys were weighed, and organ indices were calculated comparing to their body weights. These tissues were immediately preserved for GSH, MDA, NOx estimations. Chronic L-NAME treatment raised BPs, BPm, and BPd, respectively, above the normal. Treatment also increased NOx in plasma, significantly decreased it in the heart, and tended to increase it in kidney. L-NAME caused GSH depletion in the heart and kidney tissues with a concomitant increase in MDA contents in both the tissues. Plasma creatinine doubled in L-NAME-treated animals. Plasma ACE activity showed a nonsignificant decrease below control. Concurrent treatment with losartan almost completely inhibited any rise in blood pressure. Losartan replenished the partly depleted cardiac and renal antioxidant GSH and ameliorated the increase of oxidative stress damage index, MDA. However, losartan alone did not change appreciably the plasma level or cardiac and renal contents of NO,. Losartan plus L-NAME treatment caused an increase in plasma ACE activity above control. Furthermore, losartan ameliorated the L-NAME induced increase in creatinine back to value nonsignificantly different from control.
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PMID:Effects of losartan on blood pressure, oxidative stress, and nitrate/nitrite levels in the nitric oxide deficient hypertensive rats. 1598 79

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.
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PMID:Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury. 1608 42

An increase in reactive oxygen species has been shown to play a role in perpetuating hypertension and cerebral injury in stroke-prone spontaneously hypertensive rats (SHRsp). Lipid peroxidation in the cerebral cortex is much more intense in SHRsp after establishment of severe hypertension as compared to that in normotensive Wistar-Kyoto rats (WKY). Cortical neurons from SHRsp are more vulnerable to hypoxia and hyponutritional conditions. We sought to investigate whether long-term administration of seleno-glutathione peroxidase mimic ebselen (PZ51) would have a protective effect on cortical neurons in SHRsp, and, if so, the possible mechanisms of this effect. Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and control group. Age-matched WKY were used as normal controls. We examined the levels of malonaldehyde (MDA) and nitric oxide (NO) in the cerebral cortex (CC) homogenate, detected the three isoforms of nitric oxide synthase (NOS) by Western blotting, and examined cortical neurons by transmission electron microscopy. The results showed that PZ51 treatment significantly decreased both MDA and NO in the CC, inhibited inducible nitric oxide synthase (iNOS) protein expression, and alleviated the damage to cortical neurons compared to the findings for the control group. In conclusion, the present study showed that PZ51 administration suppressed lipid peroxidation and inhibited iNOS protein expression in CC homogenate, and it was suggested that these mechanisms may play a role in the protective effects of PZ51 on cortical neurons of SHRsp.
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PMID:Protective effect of antioxidant ebselen (PZ51) on the cerebral cortex of stroke-prone spontaneously hypertensive rats. 1609 69

A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 +/- 2 mm Hg vs. control, 137 +/- 2 mm Hg, P < 0.05). Blood glucose (HF, 155 +/- 4 mg/dL vs. control, 123 +/- 5 mg/dL, P < 0.05), insulin (HF, 232 +/- 63 pM vs. control, 60 +/- 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 +/- 0.37 nM MDA/ml vs. control 1.05 +/- 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 +/- 68 pg/ml vs. control, 112 +/- 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10(-4) M) was increased in the HF diet group (HF, 26.1 +/- 1.5 mN vs. control 22.3 +/- 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity.
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PMID:Obesity-induced hypertension develops in young rats independently of the renin-angiotensin-aldosterone system. 1651 74

Breast cancer is one of the most common malignancies diagnosed in women and it is increasing in incidence. Siegesbeckia glabrescens (SG) has been used in traditional oriental medicine to treat cardiovascular diseases such as hypertension and angina pectoris. This study examined whether or not SG could induce apoptosis in human breast carcinoma cells. The treatment of estrogen-receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cells with a variety of SG concentrations (0-1.0 mg/ml) resulted in a dose-dependent sequence of events that were marked by apoptosis. Furthermore, this apoptosis was accompanied by the cleavage of procaspase-9 and -3, and poly(ADP-ribose) polymerase (PARP) in the MCF-7 cells, and procaspase-8 and -3 and PARP in the MDA-MB-231 cells. Although, the SG-induced apoptosis was associated with a decrease in the level of Bcl-2 mRNA expression and an increase in the level of Bax mRNA expression in MCF-7 cells, there was no detectable change in the MDA-MB-231 cells. This suggests that SG might exert anti-proliferative action in human breast carcinoma cells via two different apoptotic pathways, namely an intrinsic signal in MCF-7 cells and an extrinsic signal in MDA-MB-231 cells. Therefore, regardless of the ER status, SG might be a promising pro-apoptotic agent for treating breast cancer.
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PMID:Siegesbeckia glabrescens induces apoptosis with different pathways in human MCF-7 and MDA-MB-231 breast carcinoma cells. 1668 80

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine the effect of CAPE on cadmium (Cd)-induced hypertension and cardiomyopathy in rats. In particular, nitric oxide (NO) may contribute to the pathophysiology of Cd induced cardiac impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels and nitric oxide (NO, a vasodilator) levels were used as markers Cd-induced cardiac impairment and the success of CAPE treatment. Also, the findings have been supported by the histopathologic evidences. The rats were randomly divided into three experimental groups each (12), as follows: the control group, Cd-treated group (Cd) and Cd plus CAPE-treated group (Cd+CAPE). CdCl(2) in 0.9% NaCl was administrated intraperitoneally (i.p.) with a dose of 1mg/kg/day. CAPE was co-administered i.p. a dose of 10 microM/kg for 15 days. Hypertension was found to be induced by intraperitoneal administration of Cd in a dose of 1mg/kg/day on the measurements taken 15 days later. MDA levels were increased (p<0.001) in cardiac tissue and NO levels were decreased (p<0.05) in serum in the Cd group than those of the control group had. On the other hand, there was a slight difference (increase) in MDA levels in the Cd+CAPE group than the ones in the control group (p<0.003). In addition, MDA levels were decreased and NO levels were increased in the Cd+CAPE group compared with the Cd group (p<0.001, p<0.0001, respectively). As a result, treatment with CAPE significantly reversed the increased lipid peroxidation (LPO) product, MDA, and decreased NO levels in Cd treated animals. In the histopathologic examination, a significant hypertrophy in atrial and ventricular myofibrils was observed in only Cd administered group, in comparison with the control group. There was no statistically significant difference between the CAPE given and control groups by means of atrial and ventricular myofibril diameters. In conclusion, the underlying mechanism of the myocardial hypertrophy may be related to hypertension due to inhibition of NO production in the vessels, and CAPE has a protective effect on Cd-induced hypertension mediated cardiac impairment in the rats.
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PMID:Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat. 1693 74

Growing evidences have shown that hypertension, cardiac hypertrophy and fibrosis were associated with an overactivity of NAD(P)H oxidase. It is unknown, however, which isoform of NAD(P)H oxidase yields O(2)*(-) formation in heart and aorta in two-kidney, two-clip (2K2C) hypertensive rats in vivo and thus is responsible for the development of cardiac remodeling. We examined the pathological change of NAD(P)H oxidase homologues and tested the effect of valsartan on the cardiac remodeling in 2K2C renovascular hypertensive rats. Four weeks after male Sprague-Dawley rats accepted 2K2C or sham operation, 2K2C hypertensive (>160 mmHg) rats were divided into vehicle-treated (2K2C) and valsartan (30 mg kg(-1) per day, for 6 weeks)-treated (2K2C+Val) groups, which were compared with sham-operated controls (Sham). At week 10, 2K2C hypertensive rats showed increased serum level of angiotensin II (Ang II), MDA and blood pressure (BP), obvious cardiac hypertrophy and fibrosis, increased O(2)*(-) production and NAD(P)H oxidase activity and expression in aorta and heart. The heart in 2K2C hypertensive rats preferred to use NADH as substrate while the aorta used both NADH and NADPH. Valsartan treatment decreased BP, ameliorated cardiac hypertrophy and fibrosis, decreased O(2)*(-) production and NAD(P)H oxidase activity in aorta and heart. Nox2 and Nox4 protein expression increased in heart, while Nox1 and Nox4 increased in aorta in 2K2C hypertensive rats, which were all normalized after valsartan treatment. In conclusion, these data indicate that different Nox expression might account for substrate preference and the formation of O(2)*(-) by NAD(P)H oxidase resulting from elevated Ang II in the 2K2C model contributes to the development of renovascular hypertension and subsequent cardiac remodeling.
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PMID:Contribution of different Nox homologues to cardiac remodeling in two-kidney two-clip renovascular hypertensive rats: effect of valsartan. 1732 85


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