Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) in the central nervous system inhibits sympathetic nerve activity, thereby decreasing blood pressure. It is unknown, however, whether orally administered antihypertensive treatment alters NO synthase (NOS) expression, particularly in the brain, and how changes in NOS expression affects sympathetic nerve activity. Azelnidipine, a recently developed long-acting dihydropyridine calcium channel blocker, does not cause baroreflex-induced tachycardia. The aim of the present study was to determine whether antihypertensive treatment with azelnidipine alters endothelial NOS (eNOS), neuronal NOS (nNOS), or inducible NOS (iNOS) expression in the brain, and how changes in NOS affect sympathetic nerve activity. Azelnidipine (20 mg/kg/day) or hydralazine (20 mg/kg/day) was orally administered for 30 days in stroke-prone spontaneously hypertensive rats (SHRSP). Blood pressure and heart rate were measured by the tail cuff method. Urinary norepinephrine excretion was measured as a marker of sympathetic nerve activity. Western blot analysis was performed to examine eNOS, nNOS, or iNOS expression levels in the brain (cortex, cerebellum, hypothalamus, and the brain stem), heart, and aorta. The extent of blood pressure reduction was similar between the two groups. Heart rate increased in the hydralazine-treated group but did not change in the azelnidipine-treated group. Urinary norepinephrine excretion was significantly increased only in the hydralazine-treated group. Treatment with azelnidipine significantly increased eNOS expression levels in the brain, heart, and aorta, but did not alter nNOS or iNOS expression levels. Treatment with hydralazine did not change any of the NOS expression levels. These results suggest that antihypertensive treatment with azelnidipine attenuates reflex-induced sympathetic activation and enhances eNOS expression levels in the brain as well as in the heart and aorta.
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PMID:Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity. 1719 Jul 27

Azelnidipine is a new dihydropyridine calcium channel blocker that causes minimal stimulation of the sympathetic nervous system despite its significant depressor effect. In the present study, we examined the effects of oral or intravenous administration of azelnidipine on cardiovascular and renal sympathetic nerve activity (RSNA) responses to air-jet stress in conscious, unrestrained stroke-prone spontaneously hypertensive rats. Oral administration of high-dose azelnidipine (10 mg/kg per day) or nicardipine (150 mg/kg per day) for 10 days caused a significant and comparable decrease in blood pressure, but low-dose azelnidipine (3 mg/kg per day) did not. Air-jet stress increased mean arterial pressure (MAP), heart rate (HR) and RSNA. High-dose azelnidipine significantly attenuated the increases in MAP, HR and RSNA in response to air-jet stress while nicardipine did not. Low-dose azelnidipine significantly attenuated the pressor response with a trend of decrease in RSNA. Intravenous injection of azelnidipine induced a slowly developing depressor effect. To obtain a similar time course of decrease in MAP by azelnidipine, nicardipine was continuously infused at adjusted doses. Both drugs increased HR and RSNA significantly, while the change in RSNA was smaller in the azelnidipine group. In addition, intravenous administration of azelnidipine attenuated the responses of MAP, HR, and RSNA to air-jet stress; by comparison, the inhibitory actions of nicardipine were weak. In conclusion, oral or intravenous administration of azelnidipine inhibited cardiovascular and sympathetic responses to air-jet stress. This action of azelnidipine may be mediated at least in part by the inhibition of the sympathetic nervous system.
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PMID:Azelnidipine attenuates cardiovascular and sympathetic responses to air-jet stress in genetically hypertensive rats. 1754 Dec 15

The long-acting dihydropyridine calcium channel blocker, azelnidipine, is suggested to inhibit sympathetic nerve activity. We previously demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM) activates sympathetic nerve activity. The aim of the present study was to determine whether oral administration of azelnidipine inhibits sympathetic nerve activity and if so to determine whether the effect is mediated by antioxidant effect in the RVLM. Azelnidipine, hydralazine, or vehicle was orally administered for 28 days to stroke-prone spontaneously hypertensive rats. Reductions in systolic blood pressure were similar in azelnidipine and hydralazine groups. Heart rate was significantly higher in the hydralazine group than in the control, but not altered in the azelnidipine group. Urinary norepinephrine excretion as an indicator of sympathetic nerve activity was significantly lower in the azelnidipine group, whereas it was significantly higher in the hydralazine group than in the control. Levels of thiobarbituric acid-reactive substances and nicotinamide adenine dinucleotide phosphate oxidase activity were significantly lower in the azelnidipine group than in control. Superoxide dismutase activity was significantly increased in the azelnidipine group more than in the control. These results suggest that azelnidipine decreases an indicator of sympathetic nerve activity by antioxidant effect mediated through inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity and activation of superoxide dismutase in the RVLM of stroke-prone spontaneously hypertensive rats.
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PMID:Azelnidipine decreases sympathetic nerve activity via antioxidant effect in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats. 1905 94

Calcium channel blockers have been widely used for the treatment of hypertension because several clinical trials have demonstrated their strong action on lowering blood pressure and their role in preventing cardiovascular events such as stroke and coronary heart disease. However, there have been few reports on the effects on cerebral hemodynamics when blood pressure is lowered with this class of drug. In this study, we used positron emission tomography and acetazolamide challenge tests to measure cerebral blood flow and cerebrovascular reserve before and after administration of a novel calcium channel blocker, azelnidipine, in nine hypertensive patients (mean age, 66.1 years) with ischemic white matter lesions. Systemic blood pressure was significantly decreased from baseline (153.8+/-15.5/92.1+/-8.5 mmHg) after treatment with azelnidipine (138.4+/-16.3/81.8+/-6.2 mmHg). The baseline global cerebral blood flow values before and after treatment were 40.1+/-7.2 mL/min/100 g and 39.2+/-8.2 mL/min/100 g, respectively. The cerebrovascular reserve values before and after treatment were 58.6+/-21.7% and 56.3+/-21.3%, respectively. Differences in these parameters were not significant. A regional analysis showed no statistical differences in regional cerebral blood flow or cerebral perfusion reserve throughout the brain before and after treatment. No associations between the decreased blood pressure and the changes in cerebral blood flow or cerebrovascular reserve were found in the whole brain or in the deep white matter with ischemic lesions. In conclusion, we found that the cerebral blood flow and cerebral vascular reserve were preserved after blood pressure lowering with azelnidipine administration in hypertensive patients with ischemic white matter lesions. Azelnidipine, a novel calcium channel blocker, could be a feasible antihypertensive regimen in terms of cerebral circulation in patients with ischemic white matter lesions.
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PMID:Hemodynamic influences of azelnidipine, a novel calcium channel blocker, on cerebral circulation in hypertensive patients with ischemic white matter lesions. 1913 4

Azelnidipine, a long-acting calcium channel blocker, is highly lipid soluble and selective for the vascular wall, and is expected to have an increasing effect on cerebral blood flow (CBF). The aim of this study is to investigate its safety and efficacy in stroke patients in the chronic stage as far as CBF is concerned using N-isopropyl-p-(123)I-iodo amphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT). The patients were orally administered 8 or 16 mg of azelnidipine. Regional CBF was evaluated by (123)I-IMP SPECT using three-dimensional stereotactic region-of-interest (ROI) template (3D-SRT), a technique using anatomical standardization and ROI template consisting of 636 ROIs for the whole brain. Mean hemispheric CBF was defined as the mean value of the corpus callosum, and the precentral, central, parietal, angular and temporal gyri. Mean hemispheric and regional CBF after 1, 3 and 6 months were analyzed using a one-way repeated-measures analysis of variance. Ten post-ischemic stroke patients with hypertension were enrolled between October 2005 and October 2007, and all of them were well controlled with normal blood pressure (before: 172.3+/-16.6/88.4+/-14.0 mm Hg; 6 months: 128.7+/-15.9/70.9+/-10.1 mm Hg). No vascular events were observed during the study period. The mean hemispheric CBF was maintained during the study period (before: 46.0+/-9.7 ml per 100 g per min; 6 months: 49.3+/-11.1 ml per 100 g per min). The regional CBF was also maintained. In the chronic stage of ischemic stroke, azelnidipine could safely decrease systemic blood pressure without decreasing CBF.
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PMID:Azelnidipine, a long-acting calcium channel blocker, could control hypertension without decreasing cerebral blood flow in post-ischemic stroke patients. A 123I-IMP SPECT follow-up study. 1987 61

As an important protective mechanism against cerebral ischemia, angiogenesis has become a topic of interest in the treatment of ischemic stroke with the challenge that few drugs promote angiogenesis. Previous studies of the identification of drug-target interactions mainly focused on the overall structures of drugs and proteins, which limited the discovery of novel structure drugs. In this article, we proposed a new strategy for discovering proangiogenic drugs based on the assumption that drug-protein interaction is mediated by substructure and domain. First, we identified substructure-domain relationships according to the known drug-protein interactions and established the drug-substructure-domain-protein relationships of genes that are proangiogenic in brain tissue and expressed significantly during ischemic stroke. Then we quantified the intensity of interaction between each drug and each protein. Finally, we obtained 540 interactive relationships between 238 drugs and 54 genes, establishing a drug-gene network with two patterns of independent and complex drug-gene interactions. Both of the patterns facilitated finding not only drugs with the same overall structure but also drugs with a different overall structure based on the same or a similar protein spectrum. In addition, we analyzed the mechanism of action of each predicted drug and extracted drugs with similar mechanisms. In vitro, our results showed that azelnidipine, azilsartan, lercanidipine, nafcillin, and vortioxetine enhanced bEnd.3 cell proliferation, migration, tube formation, and the expression of angiogenic marker PCNA. Azelnidipine, azilsartan, lercanidipine, and nafcillin increased the level of expression of proangiogenic factor VEGF. Unlike previous studies focusing on the overall structures of drugs, our research highlighted local structural similarity, which has great potential in the search for more proangiogenic drugs with novel structures.
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PMID:Discovering Proangiogenic Drugs in Ischemic Stroke Based on the Relationship between Protein Domain and Drug Substructure. 3034 17