Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase [nitric oxide (NO) synthase] was studied in rat brain both at the light and electron microscopic level with special emphasis on the vascular system. We showed that the cGMP-generating enzyme is located in cells (glial cells and pericytes) surrounding cerebral vessels, but not in the endothelium. For NO synthase, a dual localization was observed. The enzyme is present in parts of the endothelium and in nerve endings apparently innervating larger brain vessels. We propose, therefore, that NO acts on guanylate cyclase both from a "synaptic" and endothelial source.
J Cardiovasc Pharmacol 1992
PMID:Histochemistry of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase (nitric oxide synthase) in rat brain vasculature. 128 93

We determined involvement of nitric oxide (NO) derived from perivascular nerve in venous relaxation. In helical strips of dog superficial temporal veins contracted with prostaglandin F2 alpha (PGF2 alpha) nicotine produced a contraction, which was reversed to a relaxation by prazosin. The relaxation was partially attenuated by timolol or metoprolol. The residual relaxation was not influenced by treatment with atropine or indomethacin and by endothelium denudation but was abolished by NG-nitro-L-arginine (L-NA), a NO synthase inhibitor, and hexamethonium. L- but not D-arginine reversed the inhibition induced by L-NA. Relaxations induced by NO were not influenced by L-NA. Similar results were also obtained in relaxations induced by transmural electrical stimulation that were sensitive to tetrodotoxin (TTX). In the monkey venous strips, relaxations induced by nicotine under treatment with prazosin were reduced by timolol. The relaxation observed with combined treatment with alpha- and beta-antagonists was abolished by L-NA, and L-arginine restored the response. The presence of nerve fibers containing NO synthase immunoreactivity or NADPH diaphorase in the adventitia of dog and monkey veins was determined histologically. The findings so far obtained strongly suggest the presence of perivascular nerves that mediate venodilation via a release of NO. Contractions of the temporal vein appear to be mediated by norepinephrine (NE) released from adrenergic nerves that stimulates alpha 1-adrenoceptors, whereas relaxations are mediated by neurogenic NE, acting possibly on the beta 1-adrenoceptor subtype, in addition to NO derived from nerves.
J Cardiovasc Pharmacol 1995 May
PMID:Involvement of nitroxidergic and noradrenergic nerves in the relaxation of dog and monkey temporal veins. 754 70

Diabetes mellitus leads to micro- and macroangiopathy with endothelial dysfunction. To investigate the direct influence of high glucose on endothelial cell structure and possible pharmacologic effects, seven different experimental protocols were carried out on endothelial cells in culture. There were four control groups with either 5 mM D-glucose alone, 5 mM D-glucose plus 15 mM L-glucose (for osmotic control), 5 mM D-glucose plus 500 nM celiprolol, or 5 mM D-glucose plus 57 nM nitrendipine. Three experimental groups had either 20 mM D-glucose alone, 20 mM D-glucose plus 500 nM celiprolol or 20 mM D-glucose plus 57 nM nitrendipine. Treatment of all groups started at the third passage of the cells and lasted until confluence was reached (5-8 days). The endothelial cells were fixed in paraformaldehyde and stained either with hematoxylin-eosin solution, with nitro blue tetrazolium for nicotinamide adenine dinucleotide phosphate (NADPH)- diaphorase staining, or actin staining with phalloidin was carried out. For quantitative analysis of the histologic specimens, the slides were viewed via a microscope and a videocamera. The pictures were converted digitally and could be analyzed with the videopicture-analyzing system, JAVA. In the four control groups, neither treatment with 15 mM L-glucose nor administration of celiprolol or nitrendipine had an effect on cell, cytoplasm, and nuclear area. The number of giant or polynuclear cells and the histochemical NADPH-diaphorase activity were not altered. Incubation of endothelial cells with 20 mM D-glucose for 5-8 days resulted in a significant increase in total and cytoplasmic area, as well as in the number of giant and polynuclear cells, whereas the nuclear area and the NADPH-diaphorase activity were significantly reduced. Concomitant treatment with celiprolol was able to reverse these alterations in endothelial structure significantly but had only a weak effect on the NADPH-diaphorase. Nitrendipine had no beneficial effect on the high D-glucose-induced cell alterations. The actin staining of the control cells showed the typical actin pattern with most of the actin filaments arranged at the periphery of the cells. Administration of 20 mM D-glucose resulted in a disturbance of the actin pattern, with most of the actin filaments now arranged in the middle of the cells. However, neither celiprolol nor nitrendipine exhibited a significant influence on this altered actin structure. High D-glucose treatment over several days thus leads to severe changes in endothelial cell structure, and celiprolol may have a beneficial effect on these hyperglycemia-induced cell alterations.
J Cardiovasc Pharmacol 1997 Aug
PMID:High D-glucose induces alterations of endothelial cell structure in a cell-culture model. 926 45

Mechanisms of neurogenic vasodilatation and its modification by superoxide, acetylcholine, and vasoactive intestinal peptide (VIP) in porcine cerebral arteries were investigated. Relaxant responses to transmural electrical stimulation and nicotine of cerebral artery strips without endothelium were abolished by tetrodotoxin and hexamethonium, respectively. N(G)-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished or markedly reduced the neurogenic response but did not affect the relaxation by exogenous NO. The inhibitory effect was reversed by L-arginine. Duroquinone, a superoxide-generating agent, did not alter the relaxations induced by electrical stimulation and nicotine. However, in the strips treated with diethyldithiocarbamate, an inhibitor of copper/zinc superoxide dismutase (SOD), the responses were significantly inhibited by duroquinone. The inhibition was partially reversed by SOD. Physostigmine inhibited, but atropine potentiated, the neurogenic response. The relaxation was attenuated by acetylcholine but not by VIP. There were nerve fibers and bundles containing NADPH diaphorase in the adventitia of cerebral arteries. It appears that porcine cerebral arteries are innervated by NO synthase-containing nerves that liberate NO on excitation as a neurotransmitter to produce muscular relaxation, and the nerve function is protected by endogenous SOD from degradation of NO by superoxide anions. The neurogenic relaxation is inhibited by acetylcholine released from cholinergic nerves, possibly because of an impaired production or release of NO.
J Cardiovasc Pharmacol 1999 Jan
PMID:Neurogenic vasodilation mediated by nitric oxide in porcine cerebral arteries. 989 Mar 97

This study examined the occurrence of endothelial nitric oxide (NO)-synthase (NOS-III) in terminal mesenteric vessels and the involvement of NO in microvascular permeability. Possible effects were studied in bradykinin (BK)-induced and basal conditions. NOS expression was investigated by using NOS-III immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry on the light- and electron-microscopic levels. Permeability was examined in dissected mesenteries of male rats weighing 250-300 g. Tissue treatment was performed with BK (100 nM), sodium nitroprusside (SNP, 1 and 10 microM), L-nitroarginine (L-NA, 300 microM), BK and L-NA, BK and SNP, L-NA and SNP, as well as with BK, SNP (10 microM), and the guanylylcyclase inhibitor ODQ (10 microM), and BK and ODQ alone. Pharmacologically induced permeability changes were studied with fluorescein isothiocyanate (FITC)-dextran 70 kDa as a tracer for macromolecular transport. Video images were analyzed with computer determination of integrated optical density (IOI). Results were statistically verified by analysis of variance and t test. Microvascular permeability was increased by 168% after BK treatment and was enhanced by NO-synthesis inhibition with L-NA by 607%. However, the NO donor SNP led to a reduced tracer extravasation to 105 and 58%, respectively, an effect blocked by ODQ. Under basal conditions without prior BK induction, L-NA also causes an increase of IOI by 25%, whereas coapplication with SNP resulted in only a 10% increase of permeability. These results point out that NO has a modulatory role for microvascular permeability by supporting the barrier function of the endothelial lining in stimulated and nonstimulated conditions.
J Cardiovasc Pharmacol 1999 Jun
PMID:Nitric oxide decreases microvascular permeability in bradykinin stimulated and nonstimulated conditions. 1036 98

Radiofrequency ablation (RFA) can be a therapeutic option in medically inoperable lung cancer patients. In this study, we evaluated a prototype bipolar RFA device applicator that can be deployed from a standard endobronchial ultrasound (EBUS) bronchoscope to determine feasibility and histopathological analysis in animal models. Rabbit lung cancers were created by transbronchial injection of VX2 rabbit cancer cells. Once the tumors were developed, they were ablated transpleurally, under EBUS guidance using the prototype RFA device. The animals were then sacrificed for specimen resection. Pig inflammatory lung pseudo-tumors and lymphadenopathy were created by transbronchial injection of a talc paste and ablated transbronchially under EBUS guidance. Pigs were evaluated at 5 days, 2 weeks, and 4 weeks following ablation by bronchoscopy and cone beam computed tomography before necropsy. Nicotinamide adenine dinucleotide hydrogen diaphorase staining was employed to measure the ablation area. Twenty-four VX2 rabbit tumors were ablated. The total ablated area ranged from 0.6 to 3.0 cm2 (mean: 1.8 cm2), corresponding to a total energy range of 1 to 6 kJ. Six pig lung pseudo-tumors and 5 mediastinal lymph nodes were ablated. Adjacent airway ulceration was observed in 3 ablations of lymph nodes. These airway complications resolved within 4 weeks of RFA without any treatment. There was no hemoptysis, air embolism, respiratory distress, or other serious complication noted. In these 2 animal models, we provide evidence that EBUS-guided bipolar RFA is feasible and histopathology shows that can ablate lung tumors and mediastinal lymph nodes under real-time ultrasound guidance.
Semin Thorac Cardiovasc Surg
PMID:Endobronchial Ultrasound-Guided Radiofrequency Ablation of Lung Tumors and Mediastinal Lymph Nodes: A Preclinical Study in Animal Lung Tumor and Mediastinal Adenopathy Models. 3211 9