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

Left ventricular performance has been studied in 50 patients affected by primary polycythemia (P.V.) by determining systolic time intervals. 50 normal subjects were used as control group. All cases underwent a pharmacodynamic test with Amyl Nitrite. The results indicate that patients with P.V. present an abnormal behaviour of left ventricular performance after Amyl Nitrite; this alteration is more evident in patients with arterial hypertension. Amyl Nitrite, through its pharmacological action, causes changes in systolic time intervals and reveals a state of latent cardiac failure.
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PMID:[Study of left ventricular function using systolic time intervals in a group of patients with polycythemia vera (Vaquez-Osler disease)]. 615 Nov 50

Our goal was to determine whether angiotensin II (Ang II) and its metabolic fragments release nitric oxide and the mechanisms by which this occurs in blood vessels from the canine heart. We incubated 20 mg of microvessels or large coronary arteries in phosphate-buffered saline for 20 minutes and measured nitrite release. Nitrite release increased from 27 +/- 2 up to 103 +/- 5, 145 +/- 17, 84 +/- 4, 107 +/- 16, and 54 +/- 4 pmol/mg (P < .05) in response to 10(-5) mol/L of Ang I, II, III, IV, and Ang-(1-7), respectively. The effects of all angiotensins were blocked by N omega-nitro-L-arginine methyl ester (100 mumol/L), indicating that nitrite was a product of nitric oxide metabolism, and by Hoe 140 (10 mumol/L), a specific bradykinin B2 receptor antagonist, indicating a potential role for local kinin formation. The protease inhibitors aprotinin (10 mumol/L) and soybean trypsin inhibitor, which block local kinin formation, inhibited nitrite release by all of the angiotensins. Angiotensin nonselective (saralasin), type 1-specific (losartan), and type 2-specific (PD 123319) receptor antagonists abolished the nitrite released in response to all the fragments. Angiotensin type 1 and type 2 and receptors mediate nitrite release after Ang I, II, III, and Ang-(1-7), whereas only type 2 receptors mediate nitrite release after Ang IV. Similar results were obtained in large coronary arteries. In summary, formation of nitrite from coronary microvessels and large arteries in the normal dog heart in response to angiotensin peptides is due to the activation of local kinin production in the coronary vessel wall.
Hypertension 1995 Jul
PMID:Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. 760 20

Nitric oxide (NO) production is reduced in patients with essential hypertension and in some experimental models. We have investigated the effect of trichlormethiazide and captopril on NO synthase (NOS) activity and glomerular damage in the kidney of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats were induced with weekly injections of DOCA (30 mg/kg body weight (BW) and 1% saline in drinking water after right nephrectomy. As antihypertensive therapies, CAP (captopril, 40 mg/kg BW) and TCM (trichlormethiazide, 10 mg/kg BW) were given after induction of DOCA-salt hypertension. The increased blood pressure was significantly lowered by TCM, but not by CAP after 5 weeks. Nitrite production in kidney slices was suppressed in DOCA-salt rats, and immunoreactivity for both brain-type NOS (B-NOS) in macula densa and endothelial-type NOS (EC-NOS) in renal vessels was decreased. TCM significantly increased the nitrite production in the kidney slices and B-NOS immunoreactivity, whereas these changes were less in CAP. Glomerulosclerosis score was significantly higher in DOCA-salt rats, and TCM ameliorated renal damage more effectively than CAP. These results indicate that the reduced nitrite production in the kidney of DOCA-salt hypertensive rats was increased more effectively by trichlormethiazide than by captopril, via increased immunoreactivity for B-NOS in the macula densa, and prevented renal damage.
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PMID:Effect of trichlormethiazide and captopril on nitric oxide synthase activity in the kidney of deoxycorticosterone acetate-salt hypertensive rats. 867 52

Vasorelaxant activity induced by nitric oxide has been associated with a regulator activity on the blood pressure. In the present study we evaluated the nitric oxide contribution of the regulation of angiotensin II-induced vasoconstriction in normotensive rats and aortic coarctation-induced hypertensive rats. Renal vascular reactivity to angiotensin II was evaluated in the presence and absence of nitric oxide synthesis inhibitor; NG-nitro-L-arginine methyl ester. Nitrite concentration in perfusate was measured as an index of nitric oxide released and nitric oxide synthase activity was determined by production of 3H-L-citrulline. Renal NG-nitro-L-arginine methyl ester perfusion potentiated angiotensin II-induced vasoconstriction in normotensive rats but did not affect angiotensin II effect on hypertensive rats. The release of nitrites was lower in the kidneys from hypertensive rats than normotensive rats. Renal nitric oxide synthase activity was decreased in the hypertensive rats compared to the normotensive rats. We suggest that in normotensive rats, nitric oxide counteracts angiotensin II vasoconstrictor action, whereas, in hypertensive rats this mechanism is impaired, therefore, potentiating angiotensin II increase in vascular resistance thereby contributing to the developing of high blood pressure.
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PMID:[Role of nitric oxide in the modulation of the vascular response to angiotensin II in hypertensive rats]. 898 51

This study examined the production of nitric oxide (NO) in the renal cortex and medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin (OxyHb) at a concentration of 3 mumol/L was perfused through the dialysis system to trap tissue NO. Methemoglobin (MetHb), which was formed by NO oxidation of OxyHb in the dialysate, was spectrophotometrically assayed at 401 nm. Because the oxidation of OxyHb to produce MetHb is stoichiometric with NO, the production of NO can be determined by the rate of MetHb formation. We found that NO concentration was significantly higher (P < .05) in the medulla (57.1 +/- 5.57 nmol/L, n = 10) than in the cortex (31.2 +/- 5.7 nmol/L, n = 9). The minimal detectable NO level of this assay is approximately 10 nmol/L. Intravenous infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to three fold increase in cortical and medullary NO; NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms/kg per minute) decreased NO by 33% in the renal cortex and by 46.5% in the renal medulla. We have also compared under the same conditions the degradation products of NO, nitrite, and nitrate in the renal cortex and medulla using in vivo microdialysis combined with microtiter plate colorimetry. Nitrite/nitrate concentration was significantly higher (P < .05) in the medulla (2.7 +/- 0.6 mumol/L, n = 4) than in the cortex (2.1 +/- 0.2 mumol/L, n = 4). Infusion of L-arginine increased cortical and medullary nitrite/nitrate by 65% and 39%, respectively. L-NAME reduced cortical and medullary nitrite/nitrate by 18% and 23%, respectively. The results indicate that the OxyHb-NO microdialysis trapping technique is a highly sensitive in situ method for detecting regional tissue NO concentration and changes in the NO synthase activity in the kidney. These studies have shown that NO concentration is higher in medullary tissue than in the cortex.
Hypertension 1997 Jan
PMID:Nitric oxide in renal cortex and medulla. An in vivo microdialysis study. 903 1

The purpose of the present study was to determine whether interventions that promote kinin production or decrease kinin inactivation affect nitric oxide production in isolated canine coronary microvessels. Accordingly, bradykinin (10[-8] to 10[-5] mol/L), ramiprilat (10[-10] to 10[-8] mol/L), A23187 (10[-8] to 10[-6] mol/L), kallikrein (1 to 20 U/mL), and kininogen (0.5 to 10 microg/mL) were used to stimulate endothelium-dependent nitric oxide production. Receptor antagonists, serine protease inhibitors, and a kinin antibody were used to inactivate local kallikrein-kinin activity. Nitrite, the metabolite of nitric oxide in aqueous solution, was measured using the Griess reaction. All the agonists significantly increased nitrite release. For instance, the highest dose of bradykinin, ramiprilat, A23187, kallikrein, and kininogen markedly increased nitrite production, from 60+/-10 to 156+/-12, 153+/-11, 161+/-15, 176+/-15, and 168+/-16 pmol/mg (all P<.05), respectively. The increased nitrite production caused by these agents was not only blocked by N omega-nitro-L-arginine methyl ester (L-NAME) and HOE 140 (which blocks B2 kinin receptor) but by the kinin antibody also. For instance, nitrite production elicited by bradykinin, ramiprilat, A23187, and kininogen was reduced to 95+/-8, 87+/-8, 94+/-11, and 85+/-11 pmol/mg (all P<.05), respectively, by the kinin antibody. Carbachol-induced nitrite production (from 66+/-8 to 144+/-13) was blocked by L-NAME but not by HOE 140 or the kinin antibody. These results suggest that either increasing kininogen to promote endogenous kinin formation or inhibiting angiotensin-converting enzyme to decrease kinin breakdown, increases nitric oxide production in isolated coronary microvessels. These data indicate that a microvessel kallikrein-kinin system has an important role in the control of nitric oxide production in coronary microvessels.
Hypertension 1997 Nov
PMID:Role of endothelial kinins in control of coronary nitric oxide production. 936 63

Abnormal vascular smooth muscle (VSMC) proliferation is a key feature in diabetes-associated atherosclerotic disease. Since nitric oxide inhibits VSMC tone, migration, adhesion, and proliferation, we examined the effects of high glucose on IL-1beta-induced NO release from VSMCs in culture. Confluent smooth muscle cells, preincubated with either 5 mmol/L (mM) or 20 mmol/L (mM) glucose for 48 hours, were stimulated with IL-1beta. Nitrite was measured in the culture medium after 24 hours. IL-1beta-induced a 15-fold increase in NO production in normal glucose medium. Glucose (10 to 30 mmol/L (mM)) significantly reduced the response to IL-1beta. High glucose (20 mmol/L (mM)) inhibited IL-1beta-evoked NO production by approximately 50%. IL-1beta-stimulated [3H] citrulline-forming activity of the nitric oxide synthase (NOS) was also significantly lower in high-glucose-exposed cells, and this was reflected in diminished cellular levels of NOS protein. To assess the role of protein kinase C (PKC), membrane PKC activity was measured, and glucose (20 mmol/L (mM)) significantly increased it. Immunoblotting of the membranes revealed a glucose-induced increase in the PKC betaII isoform. 1,2-Dioctanoyl-glycerol, a PKC activator, mimicked the high-glucose effect on IL-1beta-induced NO release, while staurosporine, a PKC inhibitor, reversed it. The role of calcium in the glucose-mediated inhibition of cytokine-induced NO release was determined by treatment with BAPTA, an intracellular chelator of calcium. BAPTA partially reversed the inhibitory effects of glucose. Increasing intracellular calcium by A23187, an ionophore or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, significantly decreased IL-1beta-induced NO release and NOS expression. These results indicate that glucose-induced inhibition of IL-1beta-stimulated NO release and NOS expression may be mediated by PKC activation and increased intracellular calcium.
Hypertension 1998 Jan
PMID:Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. 945 18

We evaluated the effects of long-term treatment with amlodipine, a calcium antagonist, on nitric oxide synthase (NOS) activity and NOS messenger RNA (mRNA) expression in the left ventricle (LV) and its relation to coronary reserve, and microvascular remodeling in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Seventeen male Sprague-Dawley rats were given L-NAME (60 mg/kg/day) in drinking water for 6 weeks to induce hypertension, and then treated with amlodipine (L-NAME + A, 5 mg/kg/day, n = 9), or a vehicle (L-NAME + V, n = 8) for 4 weeks. Age-matched rats (C, n = 8) served as the control group. An increased blood pressure in L-NAME + V was significantly decreased in L-NAME + A. Nitrite production and endothelial cell (e) NOS mRNA in the LV were significantly decreased in L-NAME + V compared with C, and were significantly increased in L-NAME + A compared with C and L-NAME + V. L-NAME + V had a significantly decreased coronary reserve and capillary density, and a significantly increased type I collagen mRNA expression, wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and myocyte cross-sectional area. These parameters in the microvasculature were significantly improved by amlodipine. We concluded that NOS activity and eNOS mRNA were significantly increased by amlodipine in the LV of L-NAME-induced hypertensive rats, and that these increase NOS activity and eNOS mRNA expression may play a role in the amelioration of coronary reserve and microvascular remodeling.
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PMID:Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats. 1044 67

The effect of N-acetyl-L-cysteine on interleukin-1beta-induced nitric oxide synthase expression was studied in rat vascular smooth muscle cells to determine if the reduction/oxidation state would modulate cytokine-induced changes. Interleukin-1beta induced the production of nitrite, a stable metabolite of nitric oxide in a time- and dose-dependent manner. Cytokine-induced nitrite production was enhanced by the addition of N-acetyl-L-cysteine in a dose-dependent manner, with a >50% increase produced by the addition of 1 mmol/L N-acetyl-L-cysteine. There was no influence on nitrite production when the cells were treated with N-acetyl-L-cysteine alone. Northern and Western blot analyses revealed that the upregulation of interleukin-1beta-induced nitric oxide production by N-acetyl-L-cysteine resulted from an enhanced expression of inducible nitric oxide synthase. Interferon-gamma or tumor necrosis factor-alpha when used alone had no influence on nitrite production in the absence or presence of N-acetyl-L-cysteine. Nitrite accumulation was higher by the cells treated with interleukin-1beta combined with either interferon-gamma or tumor necrosis factor-alpha compared with those treated with interleukin-1beta alone. N-Acetyl-L-cysteine upregulated nitrite production and inducible nitric oxide synthase expression induced by combination treatment with interleukin-1beta and either interferon-gamma or tumor necrosis factor-alpha. However, N-acetyl-L-cysteine had no significant influence in cytokine-induced activation of nuclear factor-kappaB or signal transducer and activator of transciption-1, as assessed by electrophoretic mobility shift assays. These results demonstrate that N-acetyl-L-cysteine possibly acted as a thiol-containing reducing agent and facilitated the expression of inducible nitric oxide synthase in rat vascular smooth muscle cells by cytokines through a mechanism that is independent of nuclear factor-kappaB or signal transducer and activator of transciption-1.
Hypertension 1999 Oct
PMID:N-acetyl-L-cysteine enhances interleukin-1beta-induced nitric oxide synthase expression. 1052 29

We evaluated the effects of the kallikrein-kinin system on the proliferation and migration of primary cultured vascular smooth muscle cells (VSMCs) in vitro and neointima formation in balloon-injured rat carotid arteries in vivo. In cultured rat VSMCs, tissue kallikrein inhibited cell proliferation, and this inhibitory effect was blocked by Sar-Tyr-Aca(epsilon)-Lys [D-betaNal(7), Ile(8)]-des-Arg(9)-bradykinin, a bradykinin B(1) receptor antagonist, and by icatibant, a bradykinin B(2) receptor antagonist. Platelet-derived growth factor significantly increased the expression of the B(1) receptor but not the B(2) receptor in VSMCs. Platelet-derived growth factor-induced cell migration was significantly attenuated by des-Arg(9)-bradykinin and to a lesser degree by bradykinin. Endogenous B(1) receptor mRNA increased in rat carotid arteries after balloon angioplasty. After local delivery of adenovirus carrying the human tissue kallikrein gene into the rat carotid artery, we observed a 54% reduction in the intima/media ratio at the injured site compared with the control ratio (n=7, P:<0.01). Administration of the B(1) receptor antagonist via minipumps blocked the protective effect of kallikrein and partially reversed the intima/media ratio toward the control ratio. Kallikrein gene delivery results in the regeneration of endothelium compared with the control groups, and the B(1) receptor antagonist abolished this effect. Nitrite/nitrate, cGMP, and cAMP levels in balloon-injured arteries significantly increased after kallikrein gene delivery, whereas the B(1) receptor antagonist abolished these increases (n=4 or 5, P:<0.05). These results indicate that the B(1) receptor contributes to the reduction of neointima formation via the promotion of reendothelialization and inhibition of VSMC proliferation and migration through NO-cGMP and cAMP signaling pathways. This study provides significant implications in treating restenosis after revascularization.
Hypertension 2000 Sep
PMID:Bradykinin B(1) receptor mediates inhibition of neointima formation in rat artery after balloon angioplasty. 1098 66


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