Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The role of the heart rate modulating the decrease in cardiac output induced by the nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was investigated in anaesthetized dogs. This was achieved in dogs in which a positive pacemaker (PM) cable was located at the right ventricle. 2. The haemodynamic events were evaluated: mean arterial blood pressure (MABP), systemic vascular resistance index (SVRI), stroke volume index (SVI), heart rate (HR) and cardiac index (CI). 3. The infusion of L-NAME (0.01-10 mg kg(-1)) in the animals with the PM off caused a dose-dependent rise in MABP and SVRI, accompanied by significant decreases of HR and SVI. A resulting decrease in CI was observed at all doses of L-NAME used. 4. In the animals with the PM on, HR was maintained stable. Under this condition, the increase in MABP and SVRI as well as the decrease in SVI induced by the L-NAME infusion did not significantly differ from the PM-off animals. However, the resulting decreased CI was markedly attenuated compared to PM-off animals but significant decreases in CI were still observed at higher doses of L-NAME. 5. The results suggest that HR plays an important role in the L-NAME-mediated decreased cardiac output but other factors might also be involved.
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PMID:The role of heart rate in the modulation of the decreased cardiac output induced by acute nitric oxide synthesis inhibition in anaesthetized dogs. 1075 30

We examined characteristics of spreading depression (SD) induced on the rat cortex 1 day after transient focal ischemia. Male Wistar rats (n=21) were subjected to transient intraluminal thread occlusion of the right middle cerebral artery for 75 min. Twenty-four hours after the reperfusion, cerebral blood flow (CBF) was determined using laser Doppler flowmeter during multiple SDs elicited on both non-stroke (left) and stroke (right) cortex by the topical application of 2 M KCl. We also examined CBF responses before and after the intravenous administration of the nonspecific NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) in normal and stroke cortex. Animals were divided into two groups; Group 1 (n=12), animals with subcortical infarction and Group 2 (n=9), animals with subcortical plus cortical infarction. There were no differences between non-stroke and stroke sides in the duration or amplitude of the DC potential shifts in either group. The transient CBF hyperemia during SD was not different between non-stroke (372+/-23% of baseline, mean+/-S.E.) and stroke sides (383+/-30%) in Group 1. However, in Group 2, CBF was significantly restricted on the stroke side (192+/-15% vs. non-stroke side, 374+/-33%). In four normal animals without ischemia, there were no differences in CBF response between both sides. L-NAME had no effect on the transient CBF hyperemia during SD in any of the groups. These data suggest that the CBF responses during SD in the peri-infarction area is restricted 1 day after the transient focal ischemia, while CBF responses are intact in normal cortex overlapping a subcortical infarct. Further, our results indicate that nitric oxide does not promote CBF responses during SD in normal cortex or in tissue surrounding infarction.
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PMID:Characteristics of induced spreading depression after transient focal ischemia in the rat. 1076 Apr 93

The aim of the study was to examine the influence of a short-term treatment of conscious Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) by angiotensin II (ANG II) and by ANG II in combination with either l -NAME, HOE 140 or minoxidil on the mean arterial blood pressure (MABP) and the noradrenaline sensitivity in isolated portal vein preparations. MABP was significantly increased by ANG II treatment and ANG II plus l -NAME. However, it was slightly affected by ANG II in association with HOE 140, and significantly lowered by ANG II plus minoxidil. In control animals noradrenaline increased the frequency and the tone of contractile force. While ANG II enhanced the contractile response to noradrenaline, neither in combination with l -NAME, HOE 140 nor minoxidil prevented such an increase in the response to noradrenaline. In the presence of ergotamine, the contractile response to noradrenaline was completely blocked not only in control animals, but also in animals treated with ANG II alone or in combination with minoxidil. However, ergotamine (3 microm) failed to block completely the contractile response to noradrenaline in vessels from animals treated by ANG II in combination with l -NAME or HOE 140. These data suggest that ANG II causes an increase of noradrenaline sensitivity in the isolated portal vein of rat. l -NAME and HOE 140 unmask a contractile response to noradrenaline in the presence of ergotamine which seems to be mediated not only by alpha-adrenoceptors, but may be compensated by an endothelial relaxation.
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PMID:Short treatments of normotensive and hypertensive rats by angiotensin II and nitric oxide inhibitor induce an increase of noradrenaline sensitivity in isolated vena portae preparations. 1081 33

Chronic oral administration of l -NAME precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). The present study investigated whether acetazolamide (an acidotic agent) given alone or in combination with an angiotensin blocker (enalapril maleate) offers any protection from NO-deficient stroke in SHRSP. We also examined whether protection from NO-deficient stroke involves activation of K(+)channels. Five-week-old SHRSP drank saline (group I), l -NAME (group II), l -NAME+enalapril (group III), l -NAME+acetazolamide (group IV), and l -NAME+enalapril+acetazolamide (group V). Within a few hours following onset of stroke, rats were attached to a blood pressure recorder. In subsequent experiments, to investigate the involvement of K(+)channels, glibenclamide and BaCl(2)(K(+)channel blockers) were included in the drinking solutions that were given to the SHRSP groups receiving l -NAME, acetazolamide and enalapril. Group I of SHRSP did not develop stroke. Group II, III and IV developed stroke in 12+/-2, 29+/-2 and 20+/-2 days, respectively. SHRSP from group V did not develop stroke. However, they died in 70+/-2 days. The glibenclamide and BaCl(2)administration failed to prevent this protection from stroke. In conclusion, concurrent administration of acetazolamide and enalapril prevents onset of NO-deficient stroke in SHRSP. These stroke-protective effects are independent of reductions in mean or systolic blood pressures and do not involve an activation of K(+)channels.
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PMID:Acetazolamide and enalapril combination offers complete protection from nitric oxide-deficient stroke in stroke-prone spontaneously hypertensive rats. 1081 34

Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 microg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min. The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.
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PMID:Protective effects of imidapril on He-Ne laser-induced thrombosis in cerebral blood vessels of stroke-prone spontaneously hypertensive rats. 1082 69

1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in genetically hypertensive (GH) rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) and GH given L-NAME and either valsartan or enalapril. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly from age 7-12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined. 3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given L-NAME (P < 0.05). The GH L-NAME + valsartan and GH L-NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH L-NAME group. 4. Basilar arteries in GH (which are frankly hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen ratio. 5. In the GH L-NAME group, further inward remodelling occurred and the media to lumen ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH L-NAME rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II-stimulated growth was not entirely suppressed with an angiotensin-converting enzyme inhibitor or that there was a bradykinin effect with enalapril. 6. In GH with an endothelial defect induced by treatment with L-NAME, the further remodelling, together with an increased media to lumen ratio and the development of a stroke-like syndrome, indicates the NOS-inhibited GH rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.
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PMID:Basilar artery remodelling in the genetically hypertensive rat: effects of nitric oxide synthase inhibition and treatment with valsartan and enalapril. 1090 98

1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood pressure in the genetically hypertensive (GH) rat strain and NOS activity in regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH and normotensive (N) rats (n = 7-10 per group) were given N(G)-nitro-L-arginine methyl ester (L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7 weeks. Age- and weight-matched controls received water only. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By age 10 weeks, rats were killed and NOS activity was measured. 3. Some GH rats that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were killed before the end of the treatment period. 4. No difference in NOS activity was found between untreated N and GH strains but, in those that received treatment, a graded inhibition was observed with increasing L-NAME dose levels. The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS inhibition of 90% where the N strain had 73% inhibition. Similar results were seen in the other areas of the brain. 5. Left ventricular mass, weight related, was significantly greater in the GH compared with N and was further elevated by treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide synthase inhibition causing increased SBP in GH rats suggests an abnormality in the nitric oxide-L-arginine pathway in this strain.
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PMID:Effects of chronic inhibition of nitric oxide synthase in the genetically hypertensive rat. 1090 99

The role of endothelins (ET) in blood pressure elevation remains controversial. Data supporting involvement of the ET system in different forms of genetic and experimental hypertension in the rat has appeared in the literature in recent years. Production of endothelin (ET)-1 may be enhanced in several experimental rat models of hypertension. Examples of these exhibiting increased preproendothelin-1 mRNA or peptide in the vasculature include salt-sensitive forms like deoxycorticosterone (DOCA)-salt hypertension, DOCA-salt treated spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rats, and other models like stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-kidney 1 clip (1-K 1C) Goldblatt hypertensive rats. SHR, 2-kidney 1 clip (2-K 1C) Goldblatt hypertensive rats and chronic N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats do not appear to exhibit an ET-1 component. Significant vascular growth, and a hypotensive response and regression of vascular growth after treatment with an ET antagonist demonstrate the endothelin-dependency present in some hypertensive models. Severity of high blood pressure elevation, salt-sensitivity and insulin resistance may be common denominators of involvement of the ET system in hypertension. ET antagonism in hypertension may result in regression of vascular damage, prevention of stroke and renal failure and improvement of heart failure. Whether the same is true in human hypertension remains to be established.
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PMID:Endothelin: role in experimental hypertension. 1097 78

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
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PMID:Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease. 1100 50

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.
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PMID:Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. 1115 46


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