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)

The expression of nitric oxide (NO) synthases and the role of the NO cyclic GMP pathway on the migration of eosinophils from untreated patients with allergic rhinitis were investigated. Inducible NO synthase was strongly expressed in eosinophils from healthy individuals, but not in eosinophils from allergic rhinitis patients. The neuronal isoform was observed in eosinophils from each group studied, whereas no staining for the endothelial isoform was detected in either group. The chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 x 10(-7) M) and eotaxin (100 ng/ml) was significantly potentiated in allergic rhinitis eosinophils. In both groups, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1.0 mM) or 1H(1,2,4)-oxadiazolo(4,3,-a)quinoxalin-1-one (ODQ, 0.2 mM) markedly reduced the chemotaxis. The selective iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamidine (1400 W, 0.1-1.0 mM) significantly reduced the chemotaxis of eosinophils from healthy but not from allergic rhinitis subjects. The inhibition by L-NAME was restored by 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine, whereas the inhibition by ODQ was restored by dibutyryl cyclic GMP. In conclusion, both endothelial and inducible NO synthase isoforms are absent in allergic rhinitis eosinophils, suggesting that the NO cyclic GMP pathway in this cell type is maintained through the activity of a neuronal isoform.
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PMID:Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects. 1202 Jun 93

alpha-lactorphin (Tyr-Gly-Leu-Phe) lowers blood pressure in conscious adult SHR. This tetrapeptide is originally released from milk protein alpha-lactalbumin by enzymatic hydrolysis. In order to evaluate the antihypertensive mechanisms of alpha-lactorphin, the effects of the tetrapeptide on vascular function were investigated in (30-35 weeks old) spontaneously hypertensive rats (SHR) with established hypertension and age-matched normotensive Wistar-Kyoto (WKY) rats in vitro. In addition, we studied the vascular effects of another structurally related tetrapeptide, beta-lactorphin (Tyr-Leu-Leu-Phe), which originates from milk protein beta-lactoglobulin. Endothelium-dependent relaxation to acetylcholine (ACh) was reduced in mesenteric arterial preparations of SHR as compared to those of WKY. In SHR, the ACh-induced relaxation was augmented by alpha-lactorphin or beta-lactorphin. The role of nitric oxide (NO) is suggested, since this improvement was abolished by the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Simultaneous potassium channel inhibitor tetraethylammonium (TEA) elicited no additional effect on the ACh-induced relaxation. The cyclooxygenase inhibitor diclofenac did not attenuate the augmented ACh relaxation induced by alpha-lactorphin or beta-lactorphin, suggesting that endothelial vasodilatory prostanoids were not involved in the effect of the tetrapeptides. Endothelium-independent relaxation to the NO donor sodium nitroprusside (SNP) was augmented in mesenteric arterial preparations of SHR by simultaneous beta-lactorphin. The tetrapeptides did not alter vascular responses in mesenteric arteries from WKY. In conclusion, both alpha-lactorphin and beta-lactorphin improved vascular relaxation in adult SHR in vitro. The beneficial effect of alpha-lactorphin was directed towards endothelial function, whereas beta-lactorphin also enhanced endothelium-independent relaxation.
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PMID:Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats. 1210 90

Neuropeptide Y (NPY) and noradrenaline (NA) are frequently co-localized and co-released in the sympathetic nervous system. Since bradykinin (BK) is known to stimulate neurotransmitter release as NA in adrenal glands, we therefore hypothesized that BK might also be involved in the release of NPY. The effect of BK(1-9) on immunoreactive NPY (Ir-NPY) release was investigated in superfused human pheochromocytoma tissue. BK(1-9) (10(-7)-10(-5) M) was shown to induce a rapid Ir-NPY release in a concentration-dependent manner. This effect of BK(1-9) (10(-6) M) was mimicked by the B2 agonist [Phe(8)(CH(2)NH)Arg(9)]-bradykinin (10(-5) M) and blocked by the selective B2-receptor antagonist HOE140 (10(-5) M). Increasing Ir-NPY release was probably not mediated by nitric oxide (NO) since the outflow of Ir-NPY was not influenced by the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M). In presence of bapta-AM (10(-5) M), a chelator of cytosolic calcium, W7 (10(-5) M), a calmodulin inhibitor, TMB-8 (10(-5) M), a blocker of intracellular calcium mobilization and ryanodine (10(-5) M), a selective inhibitor of the Ca(2+)-induced release mechanism, the NPY release by BK(1-9) was significantly inhibited by 126%, 98%, 91%, and 94%, respectively. These results indicate that BK increased the release of NPY by the tumor acting through the interaction with the BK-B2 receptor and request intracellular calcium mobilization independently of a NO mechanism.
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PMID:Bradykinin-induced neuropeptide Y release by human pheochromocytoma tissue. 1237 99

Vascular responses to hypoxia are heterogeneous and involve the release of vasodilators substances such as nitric oxide (NO) and prostacyclin (PGI(2)). In vitro studies have shown that Vitamin K(1) modulates the release of arachidonic acid (AA) in vascular cells, and thus inhibits the capacity of blood vessels to synthesise vasodilator AA metabolites. The aim of our work was to investigate the effects of Vitamin K(1) on the hypoxia-induced vasorelaxation. Hypoxia was induced by changing the gas from 95% O(2)/5% CO(2) to a mixture containing 95% N(2)/5% CO(2). Rat carotid arteries were pre-contracted with phenylephrine (Phe, 10(-8)mol/l) and when the contraction reached a plateau, the bath was bubbled with 95% N(2)/5% CO(2) for 15 min. In intact rings, there was a total relaxation after 15 min of exposure to hypoxia. Removal of the endothelium strongly reduced hypoxia-induced relaxation. In intact rings, indomethacin and L-NAME reduced the hypoxic relaxation after 5 min of exposure but not after 10 or 15 min. Exposure of endothelium-intact rings to Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l), L-NAME+indomethacin as well as the combination of L-NAME+indomethacin+Vitamin K(1) reduced the hypoxic relaxation after 5 and 10 min of exposure but not after 15 min. At 5 x 10(-7)mol/l Vitamin K(1) did not attenuate hypoxia-induced relaxation. It was also found that Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l) inhibited ACh-induced relaxation in normoxic conditions. These results show that the effect of Vitamin K(1) on attenuating hypoxia-induced vasorelaxation is concentration-dependent and probably related to its action on endothelial cells.
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PMID:Vitamin K1 attenuates hypoxia-induced relaxation of rat carotid artery. 1245 20

The involvement of the nitric oxide synthase/soluble guanylate cyclase pathway on the modulation of phenylephrine-induced contractility in the rat vas deferens was investigated. Phenlylephrine-concentration response curves were obtained in absence and in presence of inhibitors, N(G)-Nitro-L-arginine (L-NOARG), NG-Nitro-L-arginine methyl esther (L-NAME) or N(G)-monomethyl-L-arginine (L-NMMA) or GC inhibitior, 1H-(1,2,4)-oxadiaziol-(4,3-a)quinoxalin-1-one (ODQ) or nitric oxide donor, 3-morpholinosydnonimine hydrochloride (SIN-1) alone or together with L-NMMA or ODQ. Both nitric oxide synthase and GC inhibitors reduced the Phe-Emax. SIN-1 alone did not change phenylephrine-induced responses and it could reverse the L-NMMA effect but not ODQ effect. The reduction of the phenylephrine-induced contractility obtained in consequence of the inhibition of the nitric oxide/GC pathway suggest that, in the rat vas deferens, despite its well identified relaxant properties, nitric oxide potentiates the contractility induced by adrenergic stimulation.
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PMID:Nitric oxide synthase/guanylate cyclase pathway modulates the rat vas deferens contractility induced by phenylephrine. 1253 Apr 68

The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C(27)H(24)BrCl(2)N(3)O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 micromol/l) elicited contracture and acetylcholine (ACh; 10 micromol/l) or BDPBI (0.01-10 micromol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 micromol/l) or pretreated preparations with aspirin, indomethacin (10 micromol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 micromol/l) or chloropheniramine maleate (10 micromol/l). In contrast to lower concentrations of atropine (1 micromol/l), higher concentrations of atropine (30 micromol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01-10 micromol/l), a histamine H(1) receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.
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PMID:A new isoquinolinone derivative with noble vasorelaxation activity. 1259 51

Eugenol is a natural pungent substance and the main component of clove oil, with vasorelaxant action. To elucidate some of the possible mechanisms involved in this action isometric tension was measured in aortic rings from male Wistar rats precontracted with phenylephrine (PHE, 10(-7) M) or KCl (75 mM). Responses to increasing concentrations of eugenol (10(-6)-10(-2) M) were obtained in the presence and absence of endothelium. In the presence of eugenol, dose-response curves to PHE (10(-9) to 10(-4) M) and KCl (5-125 mM) were displaced downwards. Concentration-dependent relaxation was observed in rings precontracted with PHE (10(-7) M) and KCl (75 mM). The tension increment produced by increasing external calcium concentration (0.25-3 mM) was also reduced by eugenol (300 microM) treatment. The inhibitory effects of eugenol (300 microM) were compared to those induced by nifedipine (0.01 microM), a selective Ca(2+) channel blocker, producing similar relaxant effects. Two other protocols were performed. After precontraction with PHE (10(-7) M), increasing concentrations of eugenol (10(-6)-10(-2) M) were used before and after N(w)-nitro-L-arginine (L-NAME, 10(-4) M) and methylene blue (10(-5) M) treatment. Eugenol-induced relaxation was reduced by endothelial damage (rubbing), L-NAME and methylene blue treatments. Results suggested that eugenol produces smooth muscle relaxation resulting from the blockade of both voltage-sensitive and receptor-operated channels that are modulated by endothelial-generated nitric oxide.
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PMID:Vasorelaxant effects of eugenol on rat thoracic aorta. 1264 11

The nitric oxide synthase (NOS) inhibitors, L-omega-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg and 100 mg/kg) and N(G)-nitro-L-arginine (L-NNA; 100 mg/kg) were used to investigate the role of NO on in vivo skeletal muscle and jejunal (mucosa and seromuscular layer) protein synthesis rates in normal (ie, untreated) and ethanol-dosed (75 mmol/kg body weight) rats. Fractional rates of protein synthesis, ie, percentage of protein pool renewed each day, k(s), %/d) were measured with a flooding dose of L-[(3)H-4]phenylalanine. In response to both doses of L-NAME and L-NNA, k(s) in skeletal muscle of normal rats decreased by 9% to 31% (P between <.05 and <.001). In the mucosa, k(s) was significantly reduced only by the higher dose of L-NAME (-49%, P <.001). In the seromuscular layer, k(s) was reduced by 15% to 57% (P between <.05 and <.001) in response to both doses of L-NAME and L-NNA. Ethanol dosage reduced k(s) in skeletal muscle (-35%, P <.001), and small reductions also occurred in the jejunal mucosal and seromuscular layers (-14% P <.05 and -12% P <.05, respectively). However, in the presence of L-NAME, ethanol reduced k(s) in jejunal mucosal and seromuscular layers by -35% (P <.01) and -30% (P <.01), respectively, compared with controls. This exacerbating effect of L-NAME predosage in ethanol-treated rats was not demonstrable in skeletal muscle. The data thus suggest that (1) endogenous NO facilitates constitutive skeletal muscle and jejunal protein synthesis in control animals in vivo; (2) the sensitivity of jejunal (but not skeletal muscle) protein synthesis to acute ethanol is increased when inhibitors of NOS are used. This tentatively implies that, in response to ethanol, overproduction of NO is not involved in the ethanol-induced reduction of protein synthesis in skeletal muscle or the jejunum.
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PMID:Skeletal muscle and jejunal protein synthesis in normal and ethanol-treated rats: the effect of the nitric oxide synthase inhibitors, L-omega-nitro-L-arginine methyl ester and N(G)-nitro-L-arginine in vivo. 1270 Oct 48

Low birth weight as the result of placental insufficiency increases the risk of hypertension in young adults; however, the vascular mechanisms involved are unclear. We tested the hypothesis that intrauterine fetal growth restriction caused by placental insufficiency results in low-birth-weight offspring with impaired endothelium-dependent vascular relaxation, enhanced vasoconstriction, and hypertension. The body weight and arterial pressure were measured in young (4 weeks), adolescent (8 weeks), and adult (12 weeks) male offspring of normal pregnant rats and pregnant rats with reduced uteroplacental perfusion (intrauterine growth-restricted, IUGR), and aortic strips were isolated for measurement of isometric contraction. The body weight was lower whereas the arterial pressure was higher in IUGR than normal rats at 4 weeks (113+/-3 versus 98+/-2), 8 weeks (133+/-3 versus 121+/-6), and 12 weeks (144+/-4 versus 131+/-3 mm Hg). Phe (10(-5) mol/L) caused an increase in active stress that was greater in IUGR than in normal rats at 4 weeks (12.4 versus 7.8), 8 weeks (13.3 versus 8.4), and 12 weeks (14.6 versus 9.0x10(4) N/m2). Removal of the endothelium enhanced Phe-induced stress in normal but not IUGR rats. In endothelium-intact strips, acetylcholine (ACh) caused relaxation of Phe contraction and induced nitrite/nitrate production that were smaller in IUGR than normal rats. L-NAME (10(-4) mol/L), which inhibits NO synthase, or ODQ (10(-5) mol/L), which inhibits cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe contraction in normal but not IUGR rats. Thus endothelium-dependent NO-mediated vascular relaxation is inhibited in IUGR offspring of pregnant rats with reduced uteroplacental perfusion, and this may explain the increased vascular constriction and arterial pressure in young adults with low birth weight.
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PMID:Reduced endothelial vascular relaxation in growth-restricted offspring of pregnant rats with reduced uterine perfusion. 1287 89

The effects of somatostatin on blood flow, plasma extravasation and knee joint sizes in the rat were investigated. Topical bolus administrations of somatostatin (10 pmol-100 nmol) onto the exposed rat knee joint capsules produced dose-dependent increases in knee joint blood flow with an ED(50) value of 1.7 nmol, and a maximum increase of 109.7%. The peak vasodilator response was observed at 1 min following drug administration, and it subsided at 5 min. Treatment of the rat knee with a somatostatin receptor antagonist cyclo(7-aminoheptanoul-Phe-D-Trp-Lys-Thr[Bzl] (cyclo-somatostatin; 2 x 20 nmol) significantly suppressed the somatostatin-induced vasodilator response, but treatment with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 2 x 50 nmol) or the cyclo-oxygenase inhibitor flurbiprofen (2 x 10 nmol) had no effect. Unilateral intraarticular injections of somatostatin (10 nmol) produced no change on blood flow and sizes of the rat knee joints, but elicited marked ipsilateral Evans blue extravasation. Cyclo-somatostatin at doses of 2 x 20 and 2 x 50 nmol did not affect the plasma extravasation response to somatostatin. The present findings indicate the vasodilator effect of somatostatin is mediated by receptors sensitive to cyclo-somatostatin inhibition, but its plasma extravasation effect might be mediated by somatostatin receptor types that are resistant to inhibition by cyclo-somatostatin. There is no evidence that nitric oxide and prostaglandins are involved in the somatostatin-induced vasodilator response. It is suspected that the vascular effects of somatostatin demonstrated in this study would play a part in the innate response of an inflammatory reaction.
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PMID:Characterisation of somatostatin actions on knee joint blood vessels of the rat. 1292 76


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