UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is not known whether the impairment of nitric oxide (NO)-dependent vasodilation of the aorta of diabetic rats is associated with any changes in the endothelial production of vasoactive prostanoids and endothelium-derived hyperpolarizing factor (EDHF). Therefore, we analyzed the contribution of NO, vasoactive prostanoids and EDHF to the decreased endothelium-dependent vasorelaxation in Sprague-Dawley rats at 4 and 8 weeks after diabetes mellitus induced by streptozotocin (STZ). The acetylcholine-induced (Ach) endothelium-dependent relaxation was significantly decreased in the thoracic aorta 8 weeks after the STZ-injection (Ach 10(-6) M: 73.1 +/- 7.4% and 56.7 +/- 7.9% for control and diabetic rats, respectively). The sodium nitroprusside-induced (NaNP) endothelium-independent vasodilation was also impaired in the diabetic rats (8 weeks after STZ) (NaNP 10(-8) M: 74.2 +/- 11.4% and 35.9 +/- 9.4% for control and diabetic rats, respectively). In contrast, the basal NO production, as assessed by the N omega-nitro-L-arginine methyl ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF(1 alpha) (stable metabolite of prostacyclin / prostaglandin I2 / PGI2 ), 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) and thromboxane B2 (TxB2 ) (stable metabolite of thromboxane A2 - TxA2) were significantly increased in the 8 weeks diabetic rat aorta. The EDHF-pathway did not change in the aortic endothelium during the development of STZ-induced diabetes. Our results indicate that STZ-induced diabetes mellitus did not modify the basal NO production, but induced the impairment of acetylcholine- and sodium nitroprusside-induced vasodilation in the thoracic aorta. In parallel with the impairment of NO-dependent vasodilation, the basal PGI2, 12-HHT and TxA2 synthesis were increased. The EDHF-pathway did not contribute to the endothelium-dependent relaxation either in control or diabetic aorta. The above alterations in the endothelial function may play an important role in the development of endothelial dysfunction and vascular complications of diabetes.
...
PMID:Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats. 1790 74

In many species, acetylcholine (Ach) induces coronary vasodilatation via endothelium-derived nitric oxide (NO). The aim of the present study was to examine if this rule pertains also to the coronary circulation of the mouse. We examined the involvement of NO and prostacyclin (PGI2) in the coronary flow response to Ach as compared to response to bradykinin (Bk) in hearts isolated from FVB or C57Bl/6 mice and perfused according to the Langendorff technique. In the isolated mouse heart, response to Ach consisted of two distinct phases: immediate, transient vasodilatation/vasoconstriction (less than 1 min) that differed between FVB and C57Bl/6 mice; and delayed sustained vasodilatation (up to 8 min) that was similar in FVB and C57Bl/6 mice. In FVB mice, the immediate phase of the Ach response consisted of a short-lasting vasodilatation followed by a vasoconstriction. In contrast, in C57Bl/6 mice, the immediate phase of the Ach response consisted exclusively of a short-lasting vasoconstriction. However, both in FVB and C57Bl/6 mice, the delayed vasodilatation was a major part of the coronary flow response to Ach and it was associated with an increase in 6-keto-PGF(1 alpha) concentration in the effluent. L-NAME (5 x 10(-4) M) displayed a minor effect on the delayed phase of the Ach response in either mice strain. In turn, indomethacin (10(-6) M), but not rofecoxib (5 x 10(-6)M), completely inhibited the delayed phase of the Ach response and the concomitant PGI2 release. On the other hand, vasodilatation induced by Bk was markedly inhibited by L-NAME, while it was unaffected by indomethacin in FVB as well as in C57Bl/6 mice. In summary, in the isolated mouse heart, Ach-induced coronary flow response displays an unusual biphasic nature and is mediated in major part by PGI2, but not by NO. Thus, in the isolated mouse heart, in parallel to Bk or other agents that are suited for the functional assessment of NO-dependent endothelial function, Ach should be used to assess PGI2-dependent endothelial function.
...
PMID:Prostacyclin, but not nitric oxide, is the major mediator of acetylcholine-induced vasodilatation in the isolated mouse heart. 1804 55

Prostaglandin F(2)(alpha) (PGF(2)(alpha)) released from the uterus causes alterations in luteal blood flow, reduces progesterone secretion, and induces luteolysis in the bovine corpus luteum (CL). We have recently discovered that luteal blood flow in the periphery of the mature CL acutely increases coincidently with pulsatile increases in a metabolite of PGF(2)(alpha) (PGFM). In this study, we characterized changes in regional luteal blood flow together with regional alterations in endothelial nitric oxide synthase (eNOS) expression during spontaneous luteolysis and in response to PGF(2)(alpha). Smooth muscle actin-positive blood vessels larger than 20 microm were observed mainly in the periphery of mature CL. PGF(2)(alpha) receptor was localized to luteal cells and large blood vessels in the periphery of mid-CL. PGF(2)(alpha) acutely stimulated eNOS expression in the periphery but not in the center of mature CL. Injection of the NO donor S-nitroso-N-acetylpenicillamine into CL induced an acute increase in luteal blood flow and shortened the estrous cycle. In contrast, injection of the NOS inhibitor l-NAME into CL completely suppressed the acute increase in luteal blood flow induced by PGF(2)(alpha) and delayed the onset of luteolysis. In conclusion, PGF(2)(alpha) has a site-restricted action depending on not only luteal phase but also the region in the CL. PGF(2)(alpha) stimulates eNOS expression, vasodilation of blood vessels, and increased luteal blood flow in periphery of mature CL. Furthermore, the increased blood flow is mediated by NO, suggesting that the acute increase in peripheral blood flow to CL is one of the first physiological indicators of NO action in response to PGF(2)(alpha).
...
PMID:Prostaglandin F2alpha increases endothelial nitric oxide synthase in the periphery of the bovine corpus luteum: the possible regulation of blood flow at an early stage of luteolysis. 1829 10

The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by N(omega)-nitro-L-arginine methyl ester (L-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1 approximately 5 mg/ml for 4 wk) and treated or not with L-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF(2alpha) expression in the alveolar septa compared with controls (P<0.05). L-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses (P<0.01), nNOS- and iNOS-positive cells, elastic fiber content (P<0.001), and isoprostane-8-PGF(2alpha) in the alveolar septa (P<0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.
...
PMID:Effects of chronic L-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation. 1835 86

This study investigates the effects of chronic methionine intake on bradykinin (BK)-relaxation. Vascular reactivity experiments were performed on carotid rings from male Wistar rats. Treatment with methionine (0.1, 1 or 2 g kg(-1) per day) for 8 and 16 weeks, but not for 2 and 4 weeks, reduced the relaxation induced by BK. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ29548, a selective thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist prevented the reduction in BK-relaxation observed in the carotid from methionine-treated rats. Conversely, AH6809, a selective prostaglandin F(2alpha) (PGF(2alpha)) receptor antagonist did not alter BK-relaxation in the carotid from methionine-treated rats. The nitric oxide synthase (NOS) inhibitors L-NAME, L-NNA and 7-nitroindazole reduced the relaxation induced by BK in carotids from control and methionine-treated rats. In summary, we found that chronic methionine intake impairs the endothelium-dependent relaxation induced by BK and this effect is due to an increased production of endothelial vasoconstrictor prostanoids (possibly TXA(2)) that counteracts the relaxant action displayed by the peptide.
...
PMID:Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation induced by bradykinin in the isolated rat carotid. 1882 Oct 53

Nitric oxide (NO) and prostacyclin (PGI(2)) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGI(2) production has not been fully clear yet. Polyaspartoyl.L-arginine (PDR) is an L-arginine residue-rich compound with inhibitory effects of platelet aggregation and thrombosis. This study investigated its effects on NO production in rat aortic endothelial cells (RAECs) and observed the influence of NO on PGI(2) level in RAECs. NO concentration in the medium of RAECs was assessed with fluorometric method; 6-keto-PGF(1 alpha), the stable metabolite of PGI(2), in the medium of RAECs was measured with radioimmunoassay kits; Protein level of PGI(2) synthase in RAECs was determined by Western blot analysis. PDR (17.0 approximately 170 microg/ml, equal to 0.5 microM-5 microM) enhanced NO level in culture medium of RAEC with concentration-dependent manner (P<0.01); L-arginine (170 microg/ml, equal to 1000 microM) and 1.70 microg/ml (0.05 microM) of PDR slightly increased NO level (P>0.05). Interestingly PDR (1.70-500 microg/ml), L-arginine (17.0-170 microg/ml) significantly elevated PGI(2) levels in medium of RAECs (P<0.01), NO synthase inhibitor, N(G)-nitro L-arginine methyl ester (L-NAME), markedly inhibited the elevated PGI(2) levels by PDR and L-arginine. NO donor, sodium nitroprusside(SNP)(1-500 microM), showed the most powerful effects of increasing PGI(2) level in RAECs, which was not influenced by L-NAME. Cyclooxigenase(COX) inhibitor, indomethacin, significantly reduced elevated PGI(2) level by both PDR and SNP in RAEC medium. PDR (170 microg/ml) increased the expression of PGI(2) synthase, L-NAME partly inhibited this effect. In conclusion, PDR enhances PGI(2) synthesis in RAEC, which is attributed to its effect of NO production; the stimulating effect of PDR on PGI(2) synthesis may be mediated via COX and PGI(2) synthase.
...
PMID:Polyaspartoyl.L-arginine enhances prostacyclin synthesis in rat aortic endothelial cells. 1902 30

The relaxant effect of hydrogen sulfide (H(2)S) in the vascular tree is well established but its influence and mechanism of action in gastrointestinal smooth muscle was hardly investigated. The influence of H(2)S on contractility in mouse gastric fundus was therefore examined. Sodium hydrogen sulfide (NaHS; H(2)S donor) was administered to prostaglandin F(2alpha) (PGF(2alpha))-contracted circular muscle strips of mouse gastric fundus, before and after incubation with interfering drugs. NaHS caused a concentration-dependent relaxation of the pre-contracted mouse gastric fundus strips. The K(+) channels blockers glibenclamide, apamin, charybdotoxin, 4-aminopyridin and barium chloride had no influence on the NaHS-induced relaxation. The relaxation by NaHS was also not influenced by L-NAME, ODQ and SQ 22536, inhibitors of the cGMP and cAMP pathway, by nerve blockers capsazepine, omega-conotoxin and tetrodotoxin or by several channel and receptor blockers (ouabain, nifedipine, 2-aminoethyl diphenylborinate, ryanodine and thapsigargin). The myosin light chain phosphatase (MLCP) inhibitor calyculin-A reduced the NaHS-induced relaxation, but the Rho-kinase inhibitor Y-27632 had no influence. We show that NaHS is able to relax PGF(2alpha)-contracted mouse gastric fundus strips. The results suggest that in the mouse gastric fundus, H(2)S causes relaxation at least partially via activation of MLCP.
...
PMID:Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus. 1937 71

To determine the possible roles of tumor necrosis factor-alpha (TNFalpha) and nitric oxide (NO) in the bovine oviduct, ampulla and isthmus collected during the estrous cycle were exposed for 18 h to TNFalpha, NO donor (NONOate), NO synthase inhibitors (L-NOARG, L-NAME and AMT) and oxytocin (OT) as a positive control. Prostaglandins (PGs) and NO(2)/NO(3) in conditioned media were measured. TNFalpha stimulated PGF(2alpha) secretion on Day 0 (onset of estrus = Day 0) and Days 2-3, in both the ampulla and isthmus, but on Days 18-20 only in ampulla. TNFalpha increased PGE(2) secretion in both fragments in each phase. NONOate did not affect PGF(2alpha) secretion on Days 18-20, whereas this NO donor stimulated PGF(2alpha) secretion in both fragments on Day 0 and Days 2-3. TNFalpha increased NO(2)/NO(3) production in every examined phase in the ampulla and on Days 2-3 in the isthmus. L-NAME lowered NO(2)/NO(3) production regardless of phase or fragment. L-NOARG and AMT lowered NO(2)/NO(3) production in both fragments on Day 0 and Days 2-3. The possible role of TNFalpha, NO or PGs on the oviductal contractility during the early-luteal phase was also examined. Neither TNFalpha nor NONOate influenced contractility in either fragment. Although PGF(2alpha) stimulated the contraction in both fragments, PGE(2) decreased it. When taken together, TNFalpha seems to play some role as a modulator of PGF(2alpha) and PGE(2) production and for transferring the embryo from the oviduct to the uterus by stimulating NO production in the bovine oviduct.
...
PMID:Effects of tumor necrosis factor-alpha and nitric oxide on prostaglandins secretion by the bovine oviduct differ in the isthmus and ampulla and depend on the phase of the estrous cycle. 1959 30

Hydrogen sulfide (H(2)S) has been suggested as a gaseous neuromodulator in mammals. The aim of this study was to examine the influence of H(2)S on contractility in mouse distal colon. The effect of sodium hydrogen sulfide (NaHS; H(2)S donor) on prostaglandin F(2alpha) (PGF(2alpha))-contracted circular muscle strips of mouse distal colon was investigated. In addition, tension and cytosolic calcium concentration ([Ca(2+)](cyt)) in the mouse distal colon strips were measured simultaneously in the presence of NaHS. NaHS caused concentration-dependent relaxation of the pre-contracted mouse distal colon strips. The NaHS-induced relaxation was not influenced by the K(+) channels blockers glibenclamide, apamin, charybdotoxin, barium chloride and 4-aminopyridine. The relaxation by NaHS was also not influenced by the nitric oxide inhibitor L-NAME, by the soluble guanylate cyclase respectively adenylate cyclase inhibitors ODQ and SQ 22536, by the nerve blockers capsazepine, omega-conotoxin and tetrodotoxin or by several channel and receptor blockers (ouabain, nifedipine, 2-aminoethyl diphenylborinate, ryanodine and thapsigargin). The initiation of the NaHS-induced relaxation was accompanied by an increase in [Ca(2+)](cyt), but once the relaxation was maximal and sustained, no change in [Ca(2+)](cyt) was measured. This calcium desensitization is not related to the best known calcium desensitizing mechanism as the myosin light chain phosphatase (MLCP) inhibitor calyculin-A and the Rho-kinase inhibitor Y-27632 had no influence. We conclude that NaHS caused concentration-dependent relaxations in mouse distal colon not involving the major known K(+) channels and without a change in [Ca(2+)](cyt). This calcium desensitization is not related to inhibition of Rho-kinase or activation of MLCP.
...
PMID:Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle. 1991 33

The goal of this study was to investigate the mechanism underlaying the vasodilatory effect of paeonol, a major active element from the root bark of Chinese herbs Paeonia suffruticosa Andr. and Cynanchum paniculatum (Bunge) Kitagawa. Paeonol relaxed isolated rat aorta rings by 95.6% while the 10(-6) M forskolin-induced vasodilatation used as 100%. The EC(50) of vasodilatation by paeonol is 2.9x10(-4) M. Although paeonol exerted endothelium-independent relaxation, L-NAME treatment inhibited paeonol-induced vasodilation of endothelium intact rings, while indomethacin did not. Both L-NAME and ODQ did not affect paeonol relaxation in the rings without endothelium. In addition, paeonol markedly elevated NO generation in cultured endothelial cells. Pre-treatment of propranolol, glibenclamide, TEA and BaCl(2) did not affect paeonol relaxation of endothelium removed rings. On the other hand, pre-treated of rings (without endothelium) with paeonol markedly blocked vasoconstriction induced by AngII, PGF(2alpha), 5-HT, dopamine, vasopressin, endothelin-1 and PE. The paeonol incubation also significantly attenuated KCl-induced contraction which mainly depended on Ca(2+) influx. In Ca(2+)-free medium (containing 10(-4) M of EGTA and 60 mM of KCl), paeonol suppressed the contraction curve of CaCl(2). In addition, paeonol also inhibited contraction by PE in Ca(2+) free solution (containing 10(-4) M of EGTA) which mainly relied on intracellular Ca(2+) release. Whole-cell patch-clamp experiment showed that paeonol shifted the I-V curve and the peak value of calcium currents was significantly inhibited. In conclusion, our study suggested that voltage-dependent and receptor-operated Ca(2+) channel, as well as intracellular Ca(2+) release were all inhibited by paeonol. An intracellular Ca(2+) regulatory mechanism may be responsible to potent vasodilatory effect of paeonol.
...
PMID:Vascular dilation by paeonol--a mechanism study. 2064 26

<< Previous 1 2 3 4 5 6 Next >>