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. In pregnant rats, chronic NO-synthase inhibition induces the development of a pre-eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO-donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d-1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3. L-NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently decreased maternal blood pressure but had no effect vascular reactivity and, whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose (of molsidomine)-dependently limited the rise in maternal blood pressure induced by L-NAME alone but unexpectedly, dose-dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation-induced model of pre-eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO-donors in pre-eclamptic women.
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PMID:Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats. 898 13

The participation of nitric oxide (NO) in antinociceptive activity of molsidomine and sodium nitroprusside (SNP) was studied in mice using the writhing test. Molsidomine (300 and 150 mg/kg) and SNP (1.52-0.38 mg/kg) induced antinociception that was antagonized by naloxone. L-arginine (500-62.5 mg/kg) did not produce antinociceptive effects, whereas N omega-nitro-L-arginine methyl ester (L-NAME) (37.5-150 mg/kg) induced antinociception which was suppressed by naloxone. Methylene blue did not change the molsidomine- and SNP-induced antinociception, but significantly intensified that produced by L-NAME. L-arginine increased antinociceptive effect of molsidomine but not that of SNP. Antinociceptive activity of L-NAME was partially reversed by L-arginine. D-arginine failed to influence these effects. The present findings suggest that the NO-cGMP pathway is not involved in the mechanism of molsidomine- and SNP-induced antinociception in the writhing test in mice.
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PMID:Studies on the antinociceptive effects of sodium nitroprusside and molsidomine in mice. 956 42

Two exogenous NO donors were used to act as substitutes for impaired endogenous nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks' lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) induced stabilized hypertension. Simultaneously administered isosorbide-5-mononitrate did not prevent the development of hypertension. Molsidomine, administered concomitantly with L-NAME, significantly attenuated the BP increase. However, BP was still found to be moderately increased compared to the initial values. Remarkable alterations in the geometry of the aorta, carotid and coronary artery found in NO-deficient hypertension were prevented in rats administered L-NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the maximum hypotensive value did not differ from the values recorded in the controls or in animals treated with L-NAME plus molsidomine. Notably enough, the hypotension was similar to that found in rats administered L-NAME alone for six weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute and molsidomine substitute only partially the impaired endogenous NO production.
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PMID:Efficiency of NO donors in substituting impaired endogenous NO production: a functional and morphological study. 1152 44

Aim of this experimental study is to verify the protective effect of molsidomine on the renal function and structural modifications in the ischemia-reperfusion rat kidney. Sixty-eight male Sprague-Dawley rats, which were right nephrectomized and occluded left renal artery for 60 minutes were used. Group I (n = 10) Sham-Operated animals, which only underwent right nephrectomy. Group II (n = 20) Untreated ischemic rats, which underwent left renal ischemia by occlusion of the renal artery for 60 minutes before blood flow was restored. Group III (n = 18) Molsidomine treated ischemic rats, Group IV (n = 20) L-NAME (N(G)-nitro-L-arginine methyl ester) treated ischemic rats. Serum creatinine and blood urea nitrogen (BUN) were measured daily and biopsies were obtained from the remaining left kidneys. At seventh day, 55% and 50% of the rats remained alive at the G-II and G-IV respectively. Molsidomine treated rats (G-III) were alive and healthy at day 7. The serum creatinine and BUN levels were significantly higher in G-II and G-IV when compared with the sham-operated group (G-I). G-III rats showed a rapid return to the normal serum creatinine and BUN values on postoperative days 1, 2, 3 and 4. The obtained values in G-II were significantly lower in comparison to the values of G-II and G-IV. The most severe damage (grade 3 to 4) was determined in the kidneys of rats from GII or GIV. The degree of renal tubular damage in GIII was evaluated as grade 1 or 2 tubular damage according to Jablonkski's scale. Our findings suggested that the administration of molsidomine may vanquish the pernicious effects of warm ischemia on kidney structure and function.
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PMID:The effects of the nitric oxide donor molsidomine prevent in warm ischemia-reperfusion injury of the rat renal--a functional and histophatological study. 1198 49

The present study was designed to investigate the role of nitric oxide (NO) on recognition memory in the rat. For this purpose, the effects on memory exerted by post-training administration of the NO synthase (NOS) inhibitor N(omega)-nitro-L-argininemethylester (L-NAME) and the NO donor molsidomine were assessed by using the object recognition task. In a first dose-response study, L-NAME, at 30 but not at 10 mg/kg impaired the animals' performance, whereas at 60 mg/kg, it induced side-effects. Molsidomine, 4 mg/kg, antagonized the L-NAME-induced performance deficits. These results indicate that NO is involved in post-training memory processes.
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PMID:Molsidomine attenuates N(omega)-nitro-L-argininemethylester-induced deficits in a memory task in the rat. 1232 88

The present study was designed to investigate the role of nitric oxide (NO) on the acquisition of a recognition memory task in the rat. For this purpose, the effects on memory exerted by pre-training administration of the NO synthase inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) and the NO donor molsidomine (N-[ethoxycarbonyl]-3-[4-morpholinosydnomine]) were assessed by using the object recognition task, a working memory paradigm based on the differential exploration of a new and familiar object. In a first dose-response study, it was found that L-NAME (10, 30, and 60 mg kg(-1), i.p.) at 30 but not at 10 mg kg(-1) disrupted animals performance, whereas the dose of 60 mg kg(-1) induced side effects. Molsidomine (2 and 4 mg kg(-1), i.p.) at 4 but not at 2 mg kg(-1), antagonized the L-NAME-induced performance deficits. These results indicate that NO is involved in the acquisition of a recognition memory task.
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PMID:Molsidomine antagonizes L-NAME-induced acquisition deficits in a recognition memory task in the rat. 1264 88

It is suggested that gastrointestinal mucosal blood flow depends on a balanced release of vasoactive substances from the endothelium. The present study investigated the effects of molsidomine on the small intestine after ischemia-reperfusion (I/R) injury in four groups of 10 rats each composed: (1) SO, sham operation; (2) untreated I/R; (3) ML, I/R plus molsidomine pretreatment; (4) L-NAME, I/R plus N-omega-nitro-L-arginine methyl ester pretreatment. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileum specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histologic changes. Mean MDA levels in the SO, untreated I/R, ML, and L-NAME groups were 95.60 +/- 2.59, 136.90 +/- 4.35, 121.10 +/- 3.38, and 137.40 +/- 4.42 nmol/g wet tissue, respectively. Although the MDA level in the ML group was higher than in the SO group ( P < 0.0001), it was significantly lower compared to the untreated I/R and L-NAME groups ( P < 0.0001, P < 0.0001). Mucosal injury scores (MIS) in groups 1-4 were 0.2 +/- 0.42, 3.9 +/- 0.73, 1.5 +/- 0.70, and 4.1 +/- 0.56, respectively. In group 3 the MIS was significantly lower than in groups 2 and 4 ( P < 0.0001, P < 0.0001). Molsidomine plays a role in attenuating reperfusion injury of the small intestine by depression of tissue MDA levels and MIS and regulates post-ischemic intestinal perfusion while restoring the intestinal microcirculatory blood flow and histologic injury.
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PMID:The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine. 1278 56

There is a sex difference in the blood pressure (BP) responses to prooxidants and antioxidants in the spontaneously hypertensive rat (SHR). In contrast to males, BP in female SHR does not decrease in response to antioxidants, such as tempol or apocynin, or increase in response to the prooxidant, molsidomine. Molsidomine decreases BP and increases expression of antioxidants in male Wistar-Kyoto rats (WKY), but not male SHR. The present study tested the hypothesis that the mechanism responsible for the lack of a pressor response to molsidomine in females is due to higher endogenous nitric oxide (NO) or to compensatory upregulation of renal antioxidant enzymes. Female SHR were treated with molsidomine in the presence or absence of nitro-L-arginine methyl ester (L-NAME) for 2 wk. Molsidomine increased nitrate/nitrite (NO(x)) and F2-isoprostane (F2-IsoP) excretion, whereas L-NAME reduced NO(x) but increased F-Isop. Molsidomine and L-NAME together further reduced NO(x) and increased F2-IsoP. Molsidomine alone had no effect on BP; L-NAME alone increased BP. The combination of molsidomine and L-NAME did not increase BP above L-NAME alone levels. Whole body and renal oxidative stress increased, while renal cortical Cu,Zn-SOD expression was downregulated and catalase was upregulated by molsidomine; glutathione peroxidase expression was unaffected. These data support our previous studies suggesting that BP in female SHR is independent of either increases or decreases in oxidative stress. The mechanisms responsible for the sex difference in BP response to increase or decrease of oxidative stress are not due to increased NO in females or to compensatory upregulation of antioxidant enzymes in response to increases in oxidants.
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PMID:Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes. 2001 22