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)

Oxidative stress because of an excessive production of superoxide anion (O2*-) is associated with hypertension. The present study evaluated the hypothesis that in the rostral ventrolateral medulla (RVLM), where the premotor neurons for the maintenance of vascular vasomotor activity are located, increased O2*- contributes to hypertension in spontaneously hypertensive rats (SHR) by modulating the cardiovascular depressive actions of nitric oxide (NO). Compared with normotensive Wistar-Kyoto (WKY) rats, SHR manifested significantly increased basal O2*- production, along with reduced manganese superoxide dismutase (MnSOD) expression and activity, in the RVLM. The magnitude of hypotension, bradycardia, or suppression of sympathetic neurogenic vasomotor tone elicited by microinjection bilaterally into the RVLM of a membrane-permeable SOD mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (MnTBAP), was also significantly larger in SHR. Transfection bilaterally into the RVLM of adenoviral vectors encoding endothelial nitric oxide synthase resulted in suppression of arterial pressure, heart rate, and sympathetic neurogenic vasomotor tone in both WKY rats and SHR. Microinjection of MnTBAP into the RVLM of SHR further normalized those cardiovascular parameters to the levels of WKY rats. We conclude that an elevated level of O2*- in the RVLM is associated with hypertension in SHR. More importantly, this elevated O2*- may contribute to hypertension by reducing the NO-promoted cardiovascular depression.
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PMID:Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide. 1564 47

Moderate ethanol consumption is known to reduce the risk of cardiovascular diseases; however, chronic high dose ethanol ingestion causes cardiovascular injuries including hypertension. The dose response of ethanol-induced hypertension and associated oxidative stress response has not been well established. This study investigated the dose response of ethanol on blood pressure (BP), nitric oxide (NO) and antioxidants in the plasma of the rat. Male Fisher rats (200-250 g) were divided into five groups of six animals each and treated as follows: (1) control (5% sucrose, orally) daily for 12 weeks; (2) 20-30% ethanol (1 g kg-1, orally) daily for 12 weeks; (3) 20-30% ethanol (2 g kg-1, orally) daily for 12 weeks; (4) 20-30% ethanol (4 g kg-1, orally) daily for 12 weeks; (5) 20-30% ethanol (6 g kg-1, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week through tail-cuff method. The animals were sacrificed 12 weeks after treatments and blood was collected and analyzed. Systolic and mean BP were slightly decreased with 1 g kg-1 dose but significantly elevated with 2, 4 and 6 g kg-1 doses 7-12 weeks after ethanol ingestion. Whereas diastolic BP was significantly elevated with 4 and 6 g kg-1 doses 8-12 weeks after ethanol ingestion. Blood alcohol levels were significantly elevated with 4 and 6 g kg-1 dose of ethanol for 12 weeks. Ethanol dose-dependency increased plasma malondialdehyde (MDA) and protein carbonyl levels, while nitric oxide (NO), ratio of reduced to oxidized glutathione (GSH/GSSG) and antioxidant enzymes: copper/zinc-superoxide dismutase (CuZn-SOD) and manganese (Mn)-SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were decreased 12 weeks post-treatment. The data suggested that ethanol induces hypertension at higher doses by depleting NO and antioxidants and increasing oxidative tissue injury in rats.
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PMID:Dose response of alcohol-induced changes in BP, nitric oxide and antioxidants in rat plasma. 1568 47

A group of patients with moderate hypertension (149-150/90-99 mmHg) performed physical exercise for 3 months; we determined the oxidative stress in blood samples, by calculating the level of some antioxidative markers, the enzymes SOD, CAT, GPx, MDA and comparing the results with the values obtained from a group of healthy subjects. We found an increased oxidative stress at the hypertensive patients, with initial higher values of SOD and MDA and with lower values of CAT and GPx, compared to the normal subjects. After the 3 months of physical training, the oxidative stress improved, with decreasing activity of SOD, GPx, MDA and increasing CAT, maintaining the ratio CAT/SOD and GPx/SOD superior compared to normal subjects. The clinical study proved that after 3 months of physical exercise, there wasn't any increased oxidative stress at the hypertensive patients; however, the oxidative stress is present, proved by the values of MDA, significantly higher compared to the normal subjects.
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PMID:[Evaluation of oxidative stress and enzymatic antioxidants in medium physical training of moderate arterial hypertension]. 1568 60

L-carnitine and propionyl-L-carnitine are supplements to therapy in cardiovascular pathologies. Their effect on endothelial dysfunction in hypertension was studied after treatment with either 200 mg/kg of L-carnitine or propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Endothelial function was assessed in aortic rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors involved were characterized in the presence of the inhibitors: L-NAME, indomethacin, the TXA2/PGH2 Tp receptor antagonist ICI-192,605 and the thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on phenylephrine-induced contractions was also observed. To identify the nature of vasoactive COX-derived products, enzyme-immunoassay of incubation media was assessed. Involvement of reactive oxygen species was evaluated by incubating with superoxide dismutase and catalase. Nitric oxide production was evaluated by serum concentration of NO2+NO3.Treatment with both compounds improved endothelial function of rings from SHR without blood pressure change. Propionyl-L-carnitine increased NO participation in WKY and SHR. L-carnitine reduced endothelium-dependent responses to CCh in WKY due to an increase of TXA2 production. In both SHR and WKY, L-carnitine enhanced concentration of PGI2 and increased participation of NO. Results in the presence of SOD plus catalase show that it might be related to antioxidant properties of L-carnitine and propionyl-L-carnitine. Comparison between the effect of both compounds shows that both may reduce reactive oxygen species and increase NO participation in endothelium-dependent relaxations in SHR. However, only L-carnitine was able to increase the release of the vasodilator PGI2 and even enhanced TXA2 production in normotensive rats.
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PMID:L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: different participation of NO and COX-products. 1595 69

After stress (immobilization in cages) plasma corticosterone level in prematurely aging OXYS rats was higher, while the content of NO metabolites was much lower than in Wistar rats. Stress increased blood pressure in OXYS and Wistar rats, the maximum values were observed in control and stressed OXYS rats. The concentration of reduced glutathione in the brain of OXYS rats was lower than in Wistar rats. After immobilization the concentration of reduced glutathione decreased in animals of both strains. The concentration of oxidized protein increased by 1.5 times only in OXYS rats. SOD activity remained unchanged, but in OXYS rats this parameter was higher than in Wistar rats. It can be hypothesized that high blood pressure, low NO content, high corticosterone concentration, and stress-induced deficiency of the antioxidant system (or combined effects of these factors) contribute to the development of neurodegenerative changes in the brain of OXYS rats.
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PMID:Increased stress reactivity as a possible factor of early degenerative changes in OXYS rats. 1602 63

Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier studies have demonstrated that the increase in the vasopressin type 1 receptor induced in vascular smooth muscle cells in the presence of CsA is probably due to superoxide (Krauskopf et al., J Biol Chem 278, 41685-41690, 2003). This increase in vasopressin receptor is likely at the base of increased vascular responsiveness to vasoconstrictor hormones and hypertension induced by CsA. Here, we demonstrate that CsA produces superoxide. In addition, our data show that superoxide generation does not originate from the major cellular superoxide generating systems NAD(P)H oxidase or xanthine oxidase. Our results suggest that the side effects of CsA could be diminished with the help of SOD mimetic drugs.
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PMID:Cyclosporin A generates superoxide in smooth muscle cells. 1608 72

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.
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PMID:Cerebral vascular effects of angiotensin II: new insights from genetic models. 1609 17

Hypertension is a multi-factorial process, prevalent in developed as well as in developing countries. Different antioxidants and free radicals play an important role in cardiovascular system. In present study, total antioxidant power in terms of FRAP (ferric reducing activity of plasma), free radicals and different antioxidants have been studied in essential hypertensives (n = 50) and normal subjects (n = 50). Levels of total cholesterol, low-density lipids-cholesterol, malonialdehyde, very low-density lipids (VLDL), uric acid, plasma homocysteine and low-density lipids (LDL), were significantly higher in hypertensives as compared to normotensive. HDL-cholesterol, SOD, GPx, reduced glutahione, total glutathione, oxidized glutathione, total thiols, protein thiols, non protein thiols, RNI, total antioxidant power, vitamin A, ascorbic acid and glutahione-S-transferase (GST) were decreased significantly in normotensive. We observed significantly low nitric oxide levels in hypertensive patients. No correlation was observed between severity of disease and plasma nitric oxide levels. There was a significant decrease in plasma FRAP value in essential hypertensives as compared to normotensive controls, which showed a negative correlation with diastolic blood pressure. In conclusion, our study revealed that there was a consistent significant difference between essential hypertensives versus controls with respect to most of the parameters. These complex changes are consistent in the view that essential hypertension is associated with an abnormal level of antioxidant status compared to normal response to oxidative stress or both.
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PMID:Different antioxidants status, total antioxidant power and free radicals in essential hypertension. 1613 19

There is growing evidence that oxidative stress contributes to hypertension. Oxidative stress can precede the development of hypertension. In almost all models of hypertension, there is oxidative stress that, if corrected, lowers BP, whereas creation of oxidative stress in normal animals can cause hypertension. There is overexpression of the p22(phox) and Nox-1 components of NADPH oxidase and reduced expression of extracellular superoxide dismutase (EC-SOD) in the kidneys of ANG II-infused rodents, whereas there is overexpression of p47(phox) and gp91(phox) and reduced expression of intracellular SOD with salt loading. Several mechanisms have been identified that can make oxidative stress self-sustaining. Reactive oxygen species (ROS) can enhance afferent arteriolar tone and reactivity both indirectly via potentiation of tubuloglomerular feedback and directly by microvascular mechanisms that diminish endothelium-derived relaxation factor/nitric oxide responses, generate a cyclooxygenase-2-dependent endothelial-derived contracting factor that activates thromboxane-prostanoid receptors, and enhance vascular smooth muscle cells reactivity. ROS can diminish the efficiency with which the kidney uses O(2) for Na(+) transport and thereby diminish the P(O(2)) within the kidney cortex. This may place a break on further ROS generation yet could further enhance vasculopathy and hypertension. There is a tight relationship between oxidative stress in the kidney and the development and maintenance of hypertension.
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PMID:Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? 1618 28

Endothelial dysfunction is an early sign of atherosclerosis. Patients with risk factors for atherosclerosis (e.g., hypertension, hyperlipidemia and diabetes mellitus) often show endothelial dysfunction at early stages of atherosclerosis before cardiovascular complications develop. Clinical studies and basic researches are revealing that calcium antagonists not only protect the endothelium through their hypotensive action but also improve the endothelial function through the stimulation of NO production. Regarding the mechanism for this kind of action by nifedipine (a calcium antagonist), it seems likely that the drug stimulates SOD expression in endothelial cells through enhanced VEGF expression by vascular smooth muscle cells, and thus reduces oxidative stress, leading to increased NO production.
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PMID:[Calcium antagonists and endothelial function]. 1619 12


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