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)

This study was designed to test the hypothesis that increased pressure itself could cause endothelial dysfunction and lead to decreased nitric oxide (NO) release, partly through effects on the tissue renin angiotensin system in hypertension. Cultured endothelial cells (ECs) isolated from the aortas of WKY rats were continuously exposed to a pressure of 150 mmHg in a CO2 incubator for 72 h using a pressure system, and the NOx (NO2 and NO3) and angiotensin II (Ang II) concentrations in the supernatant were measured. An Ang II type 1 receptor (AT1R) antagonist (losartan) and an Ang II type 2 receptor (AT2R) antagonist (PD123319) were added to the medium. The expression of AT1R and AT2R mRNAs was also examined. Pressure loading significantly decreased the NO release from ECs. Concomitant administration of losartan restored NO release to the level before the application of pressure (p<0.001). This effect of losartan was blocked by simultaneous administration of PD123319, bradykinin type 2 receptor antagonist, and NO synthase inhibitor (p<0.05). The Ang II concentration was increased by pressure and was further increased by losartan. The gene expression of AT1R was not changed by pressure, but AT2R mRNA was increased almost 2-fold. These results indicate that high pressure itself attenuates NO release from ECs, and that losartan improves NO release by activating the bradykinin system via AT2R stimulation. In addition, the increase of AT2R gene expression in ECs during exposure to pressure may compensate for the reduction of NO.
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PMID:Contrasting effects of angiotensin type 1 and 2 receptors on nitric oxide release under pressure. 1245 33

The diagnostic and prognostic implication of exaggerated blood pressure response to exercise have been controversial, with opinions ranging from a benign process to a harbinger of potential cardiovascular morbidity. Endothelial dysfunction has been demonstrated in patients with atherosclerosis and as a risk factor for coronary artery disease. However, whether the cause of exercise-induced hypertension might be related to endothelial dysfunction has not been well elucidated. We evaluated endothelial function in patients who showed a systolic blood pressure > or = 210 mmHg in males and > or = 190 mmHg in females during treadmill exercise test. We measured the endothelial function of the brachial artery in 35 patients with exercise-induced hypertension, and in 35 age- and gender-matched normal control subjects, by a high resolution ultrasound technique, and the concentration of NO2-/NO3- and cyclic guanosine monophosphate (GMP). Endothelial-dependent vasodilation was impaired in patients with hypertension compared to normal controls (3.14 +/- 0.61 vs. 6.5 +/- 0.76%, p < 0.05). The extent of vasodilation was significantly correlated with age (r=-0.28, p < 0.05) and systolic blood pressure difference (r=-0.36, p < 0.05). The levels of NO2-/NO3- and cyclic GMP at maximal exercise were significantly higher than those at rest and recovery in both controls and the hypertensive group (p < 0.05). Although there was no significant difference in the increment of NO2-/NO3- during maximal exercise between the controls and hypertensive group (55 +/- 17 vs. 56 +/- 12 micro mol/L, p=NS), cyclic GMP level during maximal exercise was significantly higher in the control group than the hypertensive group (10 +/- 1.8 vs. 8.3 +/- 2.5 pmol/ml, p 0.05). Patients with exercise-induced hypertension have poor endothelium-dependent vasodilation due to an impaired nitric oxide/cyclic GMP pathway, which may play a significant role in increasing blood pressure during exercise with inadequate peripheral adjustment to changing cardiac output.
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PMID:Endothelial dysfunction and alteration of nitric oxide/ cyclic GMP pathway in patients with exercise-induced hypertension. 1470 10

The major pathway for nitric oxide scavenging in red cells involves the direct reaction of the gas with HbO2 to form nitrate and the ferric form of the protein, metHb. Because both atoms of O2 are incorporated into nitrate, this process is called NO dioxygenation (NOD). The NOD reaction involves an initial, very rapid bimolecular addition of NO to bound O2 to form a transient Fe(III)-peroxynitrite complex, which can be observed spectrally at alkaline pH. This intermediate rapidly isomerizes at pH 7 (t1/2 <== 1 ms) to metHb and NO3-, which is nontoxic and readily transported out of red cells and excreted. The rate of NO consumption by intracellular HbO2 during normal blood flow is limited by diffusion up to and into the red cells and is too slow to interfere significantly with vasoregulation. In contrast, extracellular HbO2 is highly vasoconstrictive, and the resultant hypertension is a significant side effect of most hemoglobin-based blood substitutes. The major cause of this blood pressure effect seems to be the high rate of NO dioxygenation by cell-free HbO2, which can extravasate into the vessel walls and interfere directly with NO signaling between endothelial and smooth muscle cells. This interpretation is supported by a strong linear correlation between the magnitude of the blood pressure effect caused by infusion of cross-linked recombinant hemoglobin tetramers in vivo and the rate of NO dioxygenation by these proteins measured in vitro.
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PMID:No scavenging and the hypertensive effect of hemoglobin-based blood substitutes. 1499 Mar 49

Cushing's syndrome and systemic administration of glucocorticoids are associated with hypertension, but the underlying molecular mechanism is only partially understood. We have shown previously that dexamethasone downregulates the expression of the endothelial NO synthase (eNOS) gene in human endothelial cells and in the rat and that this may contribute to the blood pressure-raising effect of the steroid [Proc. Natl. Acad. Sci. USA 96 (1999) 13357]. In the current communication, we demonstrated that dexamethasone increased mean arterial blood pressure in wild-type C-57 Bl6 mice (eNOS+/+ mice), but had no effect on blood pressure in mice with a disrupted eNOS gene (eNOS-/- mice) derived from the same strain. The NOS inhibitor ethylisothiourea, used for control purposes, showed a hypertensive effect in eNOS+/+ mice, but no such effect in eNOS-/- mice. Serum NO2-/NO3- levels, an indicator of total body NO synthesis, decreased significantly when eNOS+/+ mice were treated with dexamethasone. eNOS-/- mice had lower serum NO2-/NO3- levels per se, which were not changed significantly by dexamethasone. Dexamethasone decreased the expression of eNOS in three major organs of the mouse investigated, namely the heart, the liver, and the kidney. We conclude that the expressional downregulation of eNOS and the ensuing reduction in vascular NO production contributes to the hypertension caused by glucocorticoids.
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PMID:Dexamethasone lacks effect on blood pressure in mice with a disrupted endothelial NO synthase gene. 1505 May 33

Sodium sensitivity of blood pressure appears before hypertension in immunoglobulin A nephropathy, as glomerulosclerosis and interstitial damage progress. To find whether this sensitivity is related to NO and the renin-angiotensin system, we examined 39 such patients without hypertension after they followed a diet with an ordinary sodium level for 1 week and a sodium-restricted diet for 1 week, in random order. Patients were divided into two groups at the median of their sodium sensitivity index (<0.040, n=19; > or =0.040 mmHg/mEq per day, n=20), calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linkage of two datum points obtained during the different diets. Urinary excretion of NOx (NO2 and NO3), plasma renin activity, and serum aldosterone were measured. NOx was higher in the low-index group than in the high-index group with the ordinary sodium level, but not during sodium restriction. NOx was correlated negatively and significantly with the index with the ordinary sodium level (p=-0.406), but correlation in changes during sodium loading was not significant (p=-0.195). Changes in plasma renin activity and serum aldosterone during sodium restriction were greater in the low-index group than in the high-index group. The changes in renin activity and aldosterone were correlated negatively and significantly with the index (p=-0.573 and -0.499, respectively). These results indicate that impairment of NO synthesis and a blunted response of the renin-angiotensin system are attributable to the altered sodium sensitivity of blood pressure in patients with immunoglobulin A nephropathy.
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PMID:Blunted response of the renin-angiotensin system and nitric oxide synthesis related to sodium sensitivity in immunoglobulin A nephropathy. 1505 50

Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanylyl cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress.
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PMID:Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1618 78

We investigated the effects of a dietary astaxanthin (ASX-O) on oxidative parameters in spontaneously hypertensive rats (SHR), by determination of the level of nitric oxide (NO) end products nitrite/nitrate (NO2-/NO3-) and lipid peroxidation in ASX-O-treated SHR. Oral administration of the ASX-O significantly reduced the plasma level of NO2-/NO3- compared to the control vehicle (p<0.05). The lipid peroxidation level, however, was reduced in both ASX-O- and olive oil-treated groups. We also analyzed the post-treatment effects of ASX-O on the vascular tissues by examining the changes in the aorta and coronary arteries and arterioles. The dietary ASX-O showed significant reduction in the elastin bands in the rat aorta (p<0.05). It also significantly decreased the [wall : lumen] aerial ratio of the coronary arteries. These results suggest that ASX-O can modulate the oxidative condition and may improve vascular elastin and arterial wall thickness in hypertension.
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PMID:Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. 1659 99

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) in the placenta of the patients with pregnancy induced hypertension (PIH) was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3-, the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group (P < 0.01). The levels of placental NO2-/NO3- in PIH patients (27.53 +/- 7.48 micromol/mg) were significantly lower than in normal group (54.27 +/- 9.53 micromol/mg, P < 0.01). The activity of eNOS was significantly decreased in PIH group (12.826 +/- 3.61 U/mg) as compared with that in normal group (21.72 +/- 3.83 U/mg, P < 0.01). Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group (P < 0.01). A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH (r = -0.57, P < 0.01). It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.
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PMID:Expression of endothelial nitric oxide synthase traffic inducer in the placenta of pregnancy induced hypertension. 1696 Dec 93

The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n=14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total triglyceride (TG), free fatty acid (FFA), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO2(-)/NO3(-)) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L-arginine (L-Arg), N(omega)-nitro-L-arginine (L-NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 micromol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P<0.05). It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P<0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P<0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L-Arg and decreased when incubated with L-NNA and MB in both high-fatty acid diet groups (P<0.05, P<0.01). But no difference was found before and after incubation with L-Arg, L-NNA and MB in the control rats. In the mean time, endothelium-independent maximal vasorelaxation response of renal arteries to NTP and renal arterial contractile responses to cumulative dose of NA were assayed, and there was no difference among the three groups (P>0.05). Endothelium-dependent vasorelaxation was negatively correlated with systolic blood pressure and TG, and positively correlated with NO2(-)/NO3(-) and GIR. There was a significantly negative correlation between FFA and NO2(-)/NO3(-). The present study suggests that both high-saturated and unsaturated fatty acid diets result in hypertension associated with significantly decreased endothelium-dependent vasorelaxation, dyslipidemia and IR, and that decreased endothelium-dependent vasorelaxation induced by high fatty acid diets is associated with impaired L-Arg-NO-cGMP pathways.
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PMID:Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats. 1757 94

Inorganic nitrate (NO3(-)) and nitrite (NO2(-)) are part of the nitrogen cycle in nature. To the general public these anions are generally known as undesired residues in the food chain with potentially carcinogenic effects. Among biologists, these inorganic anions have merely been viewed as inert oxidative end products of endogenous nitric oxide (NO) metabolism. However, recent studies surprisingly show that nitrate and nitrite can be metabolized in vivo to form nitric oxide (NO) and other bioactive nitrogen oxides. This represents an important alternative source of NO especially during hypoxia when the oxygen-dependent L-arginine-NO pathway can be altered. A picture is now emerging suggesting important biological functions of the nitrate-nitrite-NO pathway with profound implications in relation to the diet and cardiovascular homeostasis. Moreover, an increasing number of studies suggest a therapeutic potential for nitrate and nitrite in diseases such as myocardial infarction, stroke, hypertension, renal failure and gastric ulcers.
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PMID:NO-synthase independent NO generation in mammals. 2049 8


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