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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the critical role of superoxide dismutase (SOD) and nitric oxide in brain injury and systemic circulation during brain ischemia, we performed bilateral carotid artery ligation (BCAL) on rats and evaluated the effects of NG-monomethyl-L-arginine (L-NMMA) and a long-acting SOD derivative (SMA-SOD). After administration of L-NMMA, specific inhibitor against nitric oxide synthase (NOS), most of BCAL rats died within 6 h while no BCAL rats without L-NMMA died at all. Administration of SMA-SOD exhibited no effect on the life span of BCAL rats. Magnetic resonance imaging (MRI) and microscopic analysis for the ischemic brain revealed that, although administration of L-NMMA showed no significant effect on the ischemic brain of BCAL rats, SMA-SOD effectively prevented the ischemic changes based on permeability edema in the frontal lobe. Measurement of changes in the blood flow of the ischemic brain revealed that administration of L-NMMA decreased the blood flow in the BCAL rats while no remarkable changes were seen after administration of SMA-SOD. Urinary secretion of NO2-/NO3-, the metabolites of nitric oxide, was increased by challenging BCAL, and the presence of L-NMMA or SMA-SOD diminished this elevation. Blood pressure was increased by performing BCAL to rats, and administration of L-NMMA showed further elevation of the blood pressure. On the contrary, administration of SMA-SOD decreased post-ischemic hypertension. These results suggest that SOD may play a protective role for brain ischemia by suppressing increased vascular permeability, while nitric oxide showed beneficial effect on the ischemic brain by increasing the blood flow in the ischemic brain.
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PMID:Role of superoxide dismutase and nitric oxide on the interaction between brain and systemic circulation during brain ischemia. 752 76

Endogenous nitric oxide plays an important role in modulation of renal hemodynamics and sodium handling, with increased nitric oxide production inducing renal vasodilation and natriuresis. In the normal rat, nitric oxide activity increases as an adaptive response to increased dietary salt intake, perhaps facilitating natriuresis and thus blood pressure homeostasis. We hypothesized that impaired nitric oxide synthetic ability would result in sensitivity to the pressor effects of high dietary salt intake. Four groups of normal Sprague-Dawley rats were observed for eight weeks: Control, 0.4% NaCl chow and tap water; Salt, 4% NaCl chow and tap water; NAME, 0.4% NaCl chow and water containing the nitric oxide synthase inhibitor, L-nitro-arginine-methylester; Salt+NAME, 4% NaCl chow and water containing L-nitro-arginine-methylester. Compared to Controls, Salt rats demonstrated a significant increase in urinary excretion rate of the stable nitric oxide metabolites, NO2 and NO3, and had no increase in blood pressure. Furthermore, Salt rats had no functional or structural evidence of renal injury. In contrast, Salt+NAME rats demonstrated a significantly higher blood pressure than NAME rats, and urinary NO2 and NO3 excretion rate did not increase despite high salt intake. After eight weeks, Salt+NAME rats had significantly impaired renal function and proteinuria. We conclude that adaptive changes in endogenous NO production play a critical role in sodium and blood pressure homeostasis. Furthermore, impaired nitric oxide synthase activity may be a pathogenetic factor in the development of salt-sensitive hypertension.
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PMID:Endogenous nitric oxide synthesis determines sensitivity to the pressor effect of salt. 752 54

Alterations in intrarenal nitric oxide (NO) formation during changes in renal arterial pressure (RAP) have been suggested as a mechanism mediating pressure natriuresis. To test this hypothesis further, we examined the relation between RAP and the urinary excretion rate of nitrate/nitrite (NO3-/NO2-; NO metabolites) in anesthetized sodium-replete dogs before (n = 9) and during (n = 6) intrarenal infusion of the NO synthesis inhibitor nitro-L-arginine (NLA; 50 micrograms.kg-1.min-1). Urinary NO3-/NO2- concentrations were measured with the Griess reaction and spectrophotometry methods after enzymatic reduction of NO3- to NO2- in the samples. During control conditions, there were decreases in the urinary NO3-/NO2- excretion rate in response to reductions in RAP (150 to 75 mm Hg; slope, 0.04 +/- 0.01 nmol.min-1.g-1.mm Hg-1) in association with decreases in urinary sodium excretion (UNaV). There was a positive correlation between changes in NO3-/NO2- excretion rate and changes in RAP (r = .48; P < .005) or UNaV (r = .59; P < .001). NLA infusion resulted in decreases in NO3-/NO2- excretion rate (4.8 +/- 1.4 to 1.0 +/- 0.3 nmol.min-1.g-1) in association with reductions in UNaV (4.3 +/- 0.3 to 0.7 +/- 0.2 microL.min-1.g-1), fractional excretion of sodium (2.9 +/- 0.2% to 0.5 +/- 0.1%), and renal blood flow (4.8 +/- 0.3 to 3.3 +/- 0.2 mL.min-1.g-1), without changes in glomerular filtration rate. Furthermore, there was a marked attenuation of the NO3-/NO2- and sodium excretory responses to alterations in RAP during NO synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Relation between pressure natriuresis and urinary excretion of nitrate/nitrite in anesthetized dogs. 753 17

In a subset of dialysis patients, erythropoietin (rHuEpo) treatment exacerbates hypertension. The mechanism of this pressor effect is unknown; however, it has been suggested that decreased endogenous nitric oxide (NO) activity may play a role. To explore this hypothesis, Sprague-Dawley rats were given rHuEpo (150 U/kg s.c. three times per week) or corresponding vehicle. Blood pressure, haematocrit, and urinary excretion of the stable NO metabolites, nitrite (NO2) and nitrate (NO3), were determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatment there was a significant increase in blood pressure and haematocrit, while in vehicle-treated rats blood pressure and haematocrit remained at basal levels. Urinary excretion of NO2+NO3 increased compared to basal in rHuEpo, but not vehicle rats. Thus in normal rats rHuEpo does have a significant pressor effect, but this is not associated with decreased activity of the endogenous NO system. Thus decreased endogenous NO activity is not responsible for rHuEpo-associated hypertension. These data further suggest that endogenous NO activity is increased in rHuEpo-treated rats, perhaps as a counter-regulatory mechanism that limits the pressor effect. Whether this mechanism is active in the setting of rHuEpo-treated chronic renal failure in humans is unknown.
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PMID:The pressor effect of recombinant human erythropoietin is not due to decreased activity of the endogenous nitric oxide system. 762 92

The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate (NO3), the known metabolites of nitric oxide, was taken as an index of nitric oxide production. Chronic renal failure rats were characterized by a low creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P < 0.001) in untreated sham-operated rats. Both L-arginine and captopril were effective in the normalization of all these parameters. The combination of L-arginine and captopril had no additive effects. The nitric oxide synthase inhibitor significantly diminished the captopril beneficial effect. It is concluded that chronic renal failure in rats is a low nitric oxide production state. The supplementation of L-arginine is shown to overcome this condition. It is suggested that the beneficial effect of captopril on chronic renal failure is through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.
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PMID:Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. 764 19

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.
Hypertension 1993 Jul
PMID:Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. 768 32

Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments NO release in PMW. We determined serum levels of nitrite/nitrate (NO2 + NO3) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW. One group (HRT-PMW, n = 13) received continuous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n = 13) did not receive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling. Serum NO2 + NO3 levels increased in HRT-PMW for the duration of the study, whereas serum NO2 + NO3 levels remained unchanged in control PMW. When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change in NO2 + NO3 levels in HRT-PMW was significantly greater compared with the change in control PMW (P = .037). Likewise, when only those samples collected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO2 + NO3 levels in the HRT-PMW group remained significant (P = .047) compared with control PMW.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study. 772 43

Nitric oxide (NO) is a potent endogenous vasodilator and plays a pivotal role in the control of vascular tone by the formation of cyclic guanosine monophosphate (GMP). Patients affected by Bartter's syndrome have lower than normal vascular reactivity with normohypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension, and it is possible that increased production of NO may be involved in maintaining this reduced vascular response and vasodilatation. We have examined this possibility by studying NO2-/NO3- and cyclic GMP urinary excretions to assess NO production in vivo in seven patients affected by Bartter's syndrome compared with seven healthy controls. A group of five patients with hypokalemia other than Bartter syndrome (pseudo-Bartters) was also included in the study to evaluate the effect of hypokalemia on NO production. NO2-/NO3- urinary excretion (0.45 +/- 0.14 v 0.25 +/- 0.04 micromol/micromol urinary creatinine [controls], P < 0.005, v 0.28 +/- 0.05 [pseudo-Bartters], P < 0.01) and cyclic GMP urinary excretion (0.057 +/- 0.028 v 0.022 +/- 0.01 micromol/micromol of urinary creatinine [controls], P < 0.009, v 0.024 +/- 0.004 [pseudo-Bartters], P < 0.02) were increased in patients with Bartter's syndrome in comparison with controls and pseudo-Bartters, and a linear correlation between these two parameters was also present (P < 0.001). We conclude that in Bartter's syndrome the increased NO2-/NO3- and cyclic GMP urinary excretions point to an increased NO synthesis, which could account for the reduced vascular response of the disease, therefore adding its role in determining the vascular hyporeactivity of Bartter's syndrome.
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PMID:Increased urinary NO2-/NO3- and cyclic guanosine monophosphate levels in patients with Bartter's syndrome: relationship to vascular reactivity. 865 Dec 41

In order to clarify the mechanism of hypertension induced by a nitric oxide (NO) synthase inhibitor, L-NG-nitro-L-arginine (LNNA), metabolites of NO, catecholamines, and hemodynamic parameters were measured during 7 days of oral administration of LNNA in rats. Control rats received either L-arginine (L-Arg) or the vehicle. systolic blood pressure, measured by the tall-cuff method was elevated throughout the period of LNNA administration, but that in the two control groups was not influenced by treatment. Heart rate decreased on the second day only in LNNA-treated rats. Although L-Arg treatment had no influence, LNNA markedly decreased the plasma level and the urinary excretion of nitrate ions (NO-3). Urinary excretion of noradrenaline was significantly decreased on the second day of LNNA administration and returned to the control level thereafter. When hemodynamic changes were measured by using radioactive microspheres, LNNA was found to increase blood pressure by markedly increasing total peripheral resistance. Cardiac output was decreased by LNNA. L-Arg, again, did not influence the hemodynamic variables as compared with the vehicle control group. The regional vascular resistance index was increased by LNNA in many tissues and organs, except the brain and the heart. Regional blood flow, on the other hand, was significantly decreased only in the liver and skin by LNNA. The marked reduction in NO3- in urine by LNNA-treatments may indicate that the measured NO3- is exclusively of endogenous origin, and that inhibition of NO production causes elevation of blood pressure by constricting peripheral arteries. Sympatholytic responses by the baroreceptor reflex were thereby evident only on the second and the third days, which was indicated by bradycardia and suppression of noradrenaline excretion into urine. These results indicate that the inhibition of NO synthase actually decreases production of endogenous NO, and that the hypertension caused by decreases in NO production is due to elevation of total peripheral vascular resistance.
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PMID:Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats. 874 11

A decreased influence of nitric oxide (NO) in the peripheral vasculature is associated with the pathophysiology of established hypertension, and some studies suggest that increased blood pressure positively correlates with decreased NO production. If so, then the increased arterial pressure in one-kidney, one-clip (1K1C) hypertensive rats should be associated with decreased circulating levels of nitrite/nitrate (NO2/NO3; stable metabolites of NO) and guanosine 3',5'-cyclic monophosphate (cGMP; mediator of NO action). We measured serum NO2/NO3 and cGMP levels in early hypertensive 1K1C (2 wk after clipping) and shamoperated one-kidney (1K) normotensive rats, treated orally with or without the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2 wk). Compared with those in 1K rats, NO2/NO3 and cGMP levels were increased in 1K1C hypertensive rats but not in 1K1C rats treated with L-NAME. NO2/NO3 and cGMP levels in L-NAME-treated 1K and 1K1C rats were similar. Compared with that in 1K rats, systolic blood pressure (SBP) was increased in 1K1C rats and in L-NAME-treated 1K and 1K1C rats. The SBP increase in L-NAME-treated 1K1C rats was more rapid than in untreated 1K1C rats. In early hypertension, increases in SBP positively correlated with increases in serum NO2/NO3 and cGMP. After 2 wk of hypertension, circulating NO2/NO3 levels gradually declined and reached prehypertension levels by the fifth week of hypertension. These results provide evidence for increased NO synthesis in early hypertensive 1K1C rats, and this increased NO could be a compensatory mechanism to slow the development of hypertension in these animals.
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PMID:Increased nitric oxide activity in early renovascular hypertension. 876 93


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