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)

Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L-arginine analogues NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L-NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.
 ...
PMID:Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery. 838 55

Pulmonary vascular resistance decreases with increased cardiac output. Because nitric oxide (NO) and prostacyclin are potent vasodilators that are released with increased shear stress, their roles in the control of pulmonary vascular pressure were evaluated using isolated blood-perfused rat and dog lungs. Lungs were perfused with an initial arteriovenous pressure gradient (Ppa-Ppv) of 15 cmH2O; Ppa and Ppv were increased by the same amount, and the flow was measured. In rat lung (n = 6), the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) decreased pulmonary blood flow by approximately 50% at the same pressure (P < 0.05), whereas the cyclooxygenase inhibitor indomethacin (n = 6) had no effect. In dog lungs (n = 6), indomethacin decreased pulmonary blood flow by approximately 50% at the same pressure gradient (P < 0.05), whereas L-NAME (n = 6) had no effect. Furthermore, the flow increase that occurs as venous and arterial pressures are elevated together (so that Ppa-Ppv is constant) was inhibited by L-NAME in rat lungs and by indomethacin in dog lungs (P < 0.05 for each). Plasma guanosine 3',5'-cyclic monophosphate (cGMP) rose with increased absolute pressure in rat lung [from 71 +/- 17 to 274 +/- 104 pM (P < 0.05)], and this increase was blocked by L-NAME. Plasma cGMP was unchanged in dog lung, but the ratio of prostacyclin to thromboxane tended to be higher.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of nitric oxide and cyclooxygenase products on vascular resistance in dog and rat lungs. 839 13

This study investigates the vasodilatory effects of endothelin-1 (ET-1) in isolated guinea pig aortic rings in vitro. Cumulative dose-response curves to ET-1 were constructed and ET-1 actions on prostaglandin F2 alpha (PGF2 alpha)-precontraction were studied in both endothelium-intact and endothelium-denuded preparations, in the presence or absence of a cyclooxygenase inhibitor (indomethacin) and/or nitric oxide inhibitors (NG-nitro-L-arginine methyl ester and hemoglobin). In endothelium-intact preparations, pretreatment with indomethacin (10(-5) M, 30 min), alone or in combination with NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), significantly augmented the constrictive responses to ET-1, whereas indomethacin, L-NAME, and hemoglobin (10(-5) M) had no significant effects in the endothelium-denuded preparations. Furthermore, in PGF2 alpha-precontracted, endothelium-intact preparations, ET-1, at a dose of 10(-9) M, induced initial relaxation followed by subsequent contraction, while it only contracted the endothelium-denuded preparations. The initial relaxation was abolished by indomethacin, but not by L-NAME or hemoglobin. In addition, this relaxation was not inhibited by a specific ETA receptor antagonist, BQ-123 (6 x 10(-6) M). In addition to the involvement of nitric oxide, these results show the involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) derived from endothelium in ET-1-induced vasorelaxation in guinea pig aorta in vitro. The results also indicate that this vasorelaxation is mediated by ETB receptor activation.
 ...
PMID:Involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta. 840 21

Endothelium-dependent relaxation of mesenteric resistance arteries of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied. Acetylcholine-induced relaxation of SHR vessels precontracted with 10 microM norepinephrine was endothelium dependent and attenuated compared with WKY vessels. The impaired response of SHR vessels was normalized by inhibition of cyclooxygenase with indomethacin. Blockade of nitric oxide synthetase with NG-nitro L-arginine methyl ester (L-NAME) or inhibition of guanylate cyclase with methylene blue attenuated acetylcholine-induced relaxation of norepinephrine-contracted SHR vessels but had no effect on WKY vessels. When vessels were precontracted with 30 nM arginine vasopressin, acetylcholine induced similar degrees of relaxation in both strains. A similar response was detected when lysine vasopressin was used to induce tone. Indomethacin had no effect on relaxation responses of SHR and WKY vessels precontracted with either form of vasopressin. L-NAME and methylene blue partially inhibited acetylcholine-induced relaxation of vasopressin-contracted vessels from both strains. Acetylcholine added at baseline did not induce contraction of vessels from either strain. It is concluded that endothelium-dependent relaxation of SHR resistance arteries is not impaired under all circumstances. Acetylcholine-induced relaxation may be suppressed in SHR resistance arteries when norepinephrine is used to induce contraction as a result of catecholamine-induced production of an endothelium-derived contracting factor. Vasopressin, on the other hand, does not elicit production of this contracting factor and may enhance the vasorelaxant action of acetylcholine in resistance arteries of both strains via actions on endothelial or vascular smooth muscle cells.
 ...
PMID:Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions. 841 84

Changes in the populations of neurotransmitter receptors involved in the control of intestinal smooth muscle function have been associated with the altered motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced gut inflammation is accompanied by an increase in alpha- and a decrease in beta-adrenoceptor numbers in guinea pig small intestine. In the present study, we investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS-induced adrenoceptor changes. Smooth muscle adrenoceptor populations, labelled by subtype-specific radioligands 6 days after TNBS, were significantly different from those of sham-treated controls: alpha 1- and alpha 2-adrenoceptor numbers increased by more than 50%, while beta-adrenoceptor numbers decreased by more than 50%. These changes, associated with severe inflammation as assessed histologically and by myeloperoxidase assay, were prevented by doxantrazole or L-NAME, and only partly by MK-886. In contrast, indomethacin did not prevent these changes. It appears then that: (a) mast cell mediators, nitric oxide and leukotrienes are likely to contribute to TNBS-induced changes in adrenoceptor populations in the guinea pig inflamed intestine; (b) there is no evidence for prostanoid involvement in this process. It was suggested that changes in smooth muscle adrenoceptor populations may be an important mechanism by which gut inflammation alters intestinal motility.
 ...
PMID:Evidence for mast cell, leukotriene and nitric oxide involvement in the regulation of the adrenoceptor number of inflamed small intestine in guinea pigs. 853 63

The main objective of this work was to study the role of potassium channels in the cholinergic relaxation of cutaneous arteries during cooling. Acetylcholine (10(-8)-10(-4) M) produced isometric concentration-dependent relaxation of precontracted segments of rabbit ear (cutaneous) and femoral (noncutaneous) arteries; this relaxation was higher at 24 degrees C (cooling) than at 37 degrees C in ear, but not in femoral, arteries. In both types of arteries, at 37 and 24 degrees C, the relaxation to acetylcholine was partially reduced by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), and the relaxation that remained after L-NAME was higher at 24 degrees C than at 37 degrees C in ear, but not in femoral, arteries. At 37 and 24 degrees C, the persistent relaxation to acetylcholine after L-NAME was further reduced by smooth muscle depolarization with medium containing a high concentration of potassium (6 x 10(-2) M), and with the nonspecific inhibitors of potassium channels tetraethylammonium (10(-2) M) or 4-aminopyridine (5 x 10(-3) M) in both ear and femoral arteries. In ear arteries, the inhibitor of high conductance calcium-activated potassium channels charybdotoxin (10(-7) M), alone or combined with L-NAME, reduced the relaxation to acetylcholine at 24 degrees C, but not at 37 degrees C. In femoral arteries, charybdotoxin alone did not modify, but combined with L-NAME reduced, the relaxation to acetylcholine at either temperature. At 37 and 24 degrees C, the inhibitor of low conductance calcium-activated potassium channels apamin (10(-7) M), the inhibitor of ATP-dependent potassium channels glibenclamide (10(-5) M) and the cyclooxygenase inhibitor meclofenamate (10(-5) M), alone or combined with L-NAME, did not modify the relaxation of both ear and femoral arteries to acetylcholine. These results suggest: (1) the cholinergic relaxation of cutaneous (ear) and noncutaneous (femoral) arteries could be mediated by endothelial nitric oxide and by activation of potassium channels, and (2) cooling increases the relaxation of cutaneous arteries to cholinergic stimulation, which may be mediated, in part, by an increased response of potassium channels.
 ...
PMID:Role of nitric oxide and potassium channels in the cholinergic relaxation of rabbit ear and femoral arteries: effects of cooling. 856 11

We have evaluated the role of nitric oxide (NO) on the cyclooxygenase pathway in mouse glial cells. Exposure of primary cultures of neonatal mouse cortical astrocytes to bacterial lipopolysaccharide (LPS; 1 microgram/ml, 18 h) caused an increase in the release of both nitrite (NO2-) and prostaglandin E2 (PGE2), products of NO synthase (NOS) and cyclooxygenase, respectively. Production of both, NO2- and PGE2 by astrocytes, was inhibited by the exposure of the NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME: 1, 10, and 100 microM) in a dose related manner. Besides, other NOS inhibitors such as Nitro L-arginine (NNA: 10(-3) M) prevented the increase in PGE2 release from LPS-stimulated astrocytes. Sodium nitroprusside (SNP; 100-200 microM) used as a NO donor caused a dose-related enhancement in the accumulation of PGE2 induced by LPS and the presence of hemoglobin blocked the SNP effects. The exposure to SNP counteracted the decrease of PGE2 production in LPS-treated astrocytes in which NO synthesis was blocked by L-NAME. In addition, SNP also enhanced the synthesis of PGE2 following exogenous arachidonic acid astrocytes exposure. Interestingly, this effect was blocked by indomethacin. Treatment of astrocytes cultures with dexamethasone (0.1, 1 microM) blocked dose-relatedly the LPS-induced release of both NO2- and PGE2. As expected, the presence of indomethacin (1, 10, and 20 microM) prevented in a dose related fashion, PGE2 production by astrocytes following exposure to LPS. These results strongly indicate that in astroglial cells, NO is able to activate the cyclooxygenase pathway.
 ...
PMID:Evidence for cyclooxygenase activation by nitric oxide in astrocytes. 856 68

The cytotoxic effects of the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 were studied in human CHP100 neuroblastoma cell cultures. Incubation of neuroblastoma cultures with gp120 (1 pM-10 nM) induces cell death which is not concentration-related. The significant cell death evoked by 10 pM gp120 was prevented by neutralization of the viral protein with a monoclonal anti-gp120 (IgG) antibody. In addition, gp120-induced cytotoxicity was inhibited by [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP37849; 100 microM), [(+/-)-3R*, 4as*, 6R*, 8aR*-6-(phosphonomethyl) decahydro-isoquinoline-3-carboxylic acid] (LY274614; 100 microM), MK801 (dizocilpine; 200 nM) and 7-chloro kynurenic acid (100 microM), selective antagonists of the NMDA receptor complex; by contrast, (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 100 microM), a non-NMDA antagonist, was ineffective. Prevention of the lethality elicited by the HIV-1 coat protein was also obtained by incubating neuroblastoma cells with gp120 in Ca(2+)-free medium. The lethal effects induced by gp120 involve activation of L-arginine-nitric oxide (NO) pathway since these were prevented by haemoglobin (10 microM), a NO-trapping agent, and by D-arginine (1 mM), the less active enantiomer of the endogenous precursor of NO synthesis. Cytoprotection was also afforded by N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM), an inhibitor of NO synthase, and this was reversed by L-arginine (1 mM). Interestingly, indomethacin and flufenamic acid (10 microM), two inhibitors of cyclooxygenase, protected neuroblastoma cells from death induced by gp120. Furthermore, indomethacin prevented the neuroblastoma cell death evoked by exposure of cultures to sodium nitroprusside (SNP; 0.2-1.6 mM), a NO donor. Finally significant cytotoxic effects were observed after incubation of neuroblastoma cells with prostaglandin E2 (0.1-10 microM). In conclusion, the present data suggest that death of human CHP100 neuroblastoma cells in culture produced by gp120 involves NO and PGE2 production.
 ...
PMID:Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase. 858 64

Anandamide (AN, arachidonyl ethanolamide) has been isolated from the brain and shown to be an endogenous ligand for the delta 9-tetrahydrocannabinol (delta 9-THC) receptor. The purpose of these studies was to determine whether AN or delta 9-THC can affect the cerebral circulation. With the use of the closed cranial window AN and delta 9-THC (10(-13)-10(-3) M) were topically applied to rabbit cerebral arterioles and effects on diameter were measured with a microscope. AN and delta 9-THC similarly induced a dose-dependent dilation starting at concentrations as low as 10(-12) M. Maximum dilation for AN was 25% and that for delta 9-THC 22%. Topical coapplication of indomethacin, a cyclooxygenase inhibitor, completely blocked dilation, whereas the free radical scavengers superoxide dismutase and catalase or the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) had no effect on AN-induced dilation. The cerebrospinal fluid level of prostaglandin E2 increased only in response to 10(-7) M and greater AN and was not affected by delta 9-THC. [3H]AN superfused through the cranial window was 20% converted to arachidonic acid. These results show that AN and delta 9-THC can modulate cerebral arterioles, likely by stimulating release and metabolism of endogenous arachidonic acid. Whether dilation is due to vasodilator eicosanoids, or other vasoactive agents whose synthesis or release is cyclooxygenase dependent, is uncertain.
 ...
PMID:Anandamide and delta 9-THC dilation of cerebral arterioles is blocked by indomethacin. 859 93

Sepsis is characterized by decreased peripheral vascular resistance, however, discrepancies exist regarding the specific secondary mediators involved. This study examined whether the presence of endotoxin (ET) is a requirement for tumor necrosis factor-alpha (TNF-alpha) to induce vasodilation of isolated skeletal muscle arterioles. First order cremasteric arterioles were isolated from male Sprague-Dawley rats, cannulated with glass micropipettes, superfused in physiologic saline, and allowed to achieve spontaneous basal tone in the absence of intraluminal flow. A 2 min exposure to TNF-alpha (.01-100 ng/mL) had no apparent effect on arteriolar diameter (95 +/- 5% after .01 ng/mL and 92 +/- 6% after 100 ng/mL, p > .05 compared with basal). However, arterioles superfused with 2.5 micrograms/mL Salmonella enteritidis ET for 1 h followed by a 2 min exposure to 100 ng/mL TNF-alpha demonstrated a dilation (to 128 +/- 12%) that became statistically significant 10 min after TNF-alpha washout (to 142 +/- 12%, p < .05). This effect was eliminated by combined inhibition of cycloxygenase (with indomethacin) and nitric oxide synthase (L-NAME). The data indicate that neither ET or TNF-alpha alone elicit a direct vasomotor effect on the isolated arteriole preparation used in these studies. However, pretreatment of the vessels with ET results in the ability of TNF-alpha to cause arteriolar dilation, possibly through a mechanism involving both cyclooxygenase and nitric oxide synthase.
 ...
PMID:Endotoxin interacts with tumor necrosis factor-alpha to induce vasodilation of isolated rat skeletal muscle arterioles. 872 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>