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)

Isolated rabbit spinal resistance-sized arteries (approximately 100 microns in diameter and approximately 3 mm long) were cannulated at both ends with glass micropipettes and perfused at constant pressure (60 mmHg). An increase of flow rate corresponding to a change of pressure gradient (delta P) ranging from 0 to 20 mmHg produced a flow-dependent vasodilation. Treatment with 50 microM aspirin or 10 microM indomethacin produced a significant reduction of the flow-dependent vasodilation only at delta P of 5 mmHg. In contrast, treatment with N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM) produced no significant change. In the presence of 10 microM indomethacin, however, 30 microM L-NAME caused a marked decrease in the arterial diameter at delta P of 5 mmHg, which was completely reversed with additional administration of 1 mM L-arginine. Acetylcholine (ACh) produced a dose-dependent increase in the arterial diameter. The ACh-induced vasodilation was significantly reduced by 10 microM indomethacin or 50 microM aspirin and partially suppressed by 30 microM L-NAME. Pretreatment with both indomethacin and L-NAME completely reduced the ACh-induced vasodilation. In the presence of 10 microM indomethacin, additional treatment with 1 mM L-arginine significantly reversed the L-NAME-induced inhibition of the ACh-mediated vasodilation. Endothelial removal with Triton X-100 significantly reduced the ACh-induced vasodilation. Isocarbacyclin (a stable prostaglandin I2 analogue), prostaglandin E2, and arachidonic acid caused a dose-dependent dilation in the small arteries. These findings suggest that prostanoids play a major role in the flow- or ACh-induced vasodilation in the rabbit spinal resistance-sized small arteries.
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PMID:Flow- and agonist-mediated nitric oxide- and prostaglandin-dependent dilation in spinal arteries. 937 56

Phosphatidylinositol 3-kinase (PI3-K) has been shown to mediate insulin and insulin-like growth factor-1 (IGF-1)-induced nitric oxide (NO) generation and, thus, vascular tone. A role for PI3-K in G-protein-coupled receptor signal transduction has also been reported. As beta2 -adrenergic vascular actions are partly dependent on NO, this study the role of PI3-K on in vitro isoproterenol (Iso)-induced endothelial cell (EC) nitric oxide synthase (NOS) activation and rat aortic vascular relaxation. Cell lysates of rat aortic EC (RAEC), exposed to Iso (10 micromol/L) for 5 minutes, were immunoprecipitated with an antiphosphotyrosine antibody prior to assay for Western blot for the p85-kd regulatory subunit of PI3-K. Endothelial NOS activity was determined by measuring nitrite production. Endothelium-intact aortic rings from male Wistar rats were preincubated with the PI3-K inhibitors, wortmannin (WT), or LY294002 (LY), precontracted with phenylepinephrine (PE), and relaxation to graded doses of Iso was measured. NO contribution to vascular relaxation was assessed by L-N(G)-nitroarginine methyl ester (L-NAME), a NOS inhibitor. Both Iso and IGF-1 induced an increase in p85 subunit phosphorylation as demonstrated by Western analysis, effects inhibited by preincubation with WT. Iso also enhanced association of p85 with the Triton X-100-insoluble fraction of RAEC, reflecting translocation of this enzyme to a cytoskeletal fraction. In addition, Iso as well as IGF-1 significantly increased eNOS activity measured by nitrite production. Both WT and LY markedly inhibited relaxation to Iso, while L-NAME nearly abolished this beta-adrenergic-mediated vasorelaxation. These data indicate that both Iso and IGF-1 activate the EC PI3-K pathway which mediates, in part, the release of NO and subsequent vasorelaxation in response to this beta-agonist Iso as well as to IGF-1.
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PMID:Phosphatidylinositol 3-kinase may mediate isoproterenol-induced vascular relaxation in part through nitric oxide production. 1188 78

The Ca2+ mobilizing peptide, bradykinin (BK), stimulates endothelial nitric oxide synthase (eNOS)-derived cellular nitric oxide (NO) production in association with altering the subcellular distribution of the enzyme. In the present study we examine the influence of cellular GTPases, particularly the large GTPase dynamin, on BK-mediated eNOS localization and cellular NO production. BK stimulation of ECV cells, which were stably transfected with eNOS-GFP (eNOS-GFP ECV304), increased NO production. This was associated with the mobilization of eNOS-GFP protein into Triton X-100-insoluble fractions of cell lysates, and an internalization of plasmalemmal eNOS-GFP in live and fixed ECV 304 cells. Incubation of digitonin-permeabilized ECV304 cells with the non-hydrolyzed GTP analog, GTP-gamma-S, abrogated the BK-mediated internalization of eNOS-GFP as assessed by confocal microscopy. Conversely, inhibition of clathrin-dependent endocytosis, via overexpression of AP 180 or pretreatment of cells with chlorpromazine, did not influence BK-mediated eNOS redistribution. Furthermore, specific inhibition of dynamin-2 GTPase function by overexpression of a dominant negative construct, K44A, prevented the BK-mediated enrichment of eNOS-GFP within low buoyant density, caveolin-enriched fractions of eNOS-GFP ECV304 cell lysates. Dynamin-2 K44A overexpression also markedly impaired BK-dependent, L-NAME-inhibited NO production as did incubation of permeabilized cells with GTP-gamma-s. These studies demonstrate that disruption of dynamin- and GTP-dependent, but clathrin-independent, vesicle trafficking pathways impairs BK-dependent cellular NO production, via inhibition of the internalization of eNOS-containing plasmalemmal vesicles.
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PMID:Inhibition of GTP-dependent vesicle trafficking impairs internalization of plasmalemmal eNOS and cellular nitric oxide production. 1287 16

Genistein, a phytoestrogen, possesses cardioprotective effects. Responses to genistein (0.1-100 microM) were assessed in 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha) (U46619)-contracted porcine coronary arterial rings, with significant relaxations at high concentrations. At concentrations with little relaxation, genistein (0.3-3 microM) did not affect relaxation produced by bradykinin and the calcium ionophore, A23187. In contrast, sodium nitroprusside- and cromakalim-induced relaxations were enhanced by genistein (3 microM). N(omega)-nitro-L-arginine methyl ester (L-NAME) (300 microM) or Triton X-100 (0.5%) did not affect the enhancement of relaxation by genistein. The tyrosine kinase inhibitor, tyrphostin 23 (30 microM), had no effect on sodium nitroprusside-elicited relaxation. In summary, genistein relaxed porcine coronary artery at relatively high concentrations. At a physiologically relevant concentration (3 microM), it is devoid of significant vascular effect, but enhanced endothelium-independent relaxations. This effect of genistein does not involve the nitric oxide synthase (NOS) pathway and the endothelium, and is mediated through a mechanism different from tyrosine kinase inhibition.
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PMID:The phytoestrogen genistein enhances endothelium-independent relaxation in the porcine coronary artery. 1464 90

Puerarin, an isoflavonoid derived from the Chinese medicinal herb Radix puerariae, has been suggested to be useful in the management of various cardiovascular disorders. The present study examined the effect of acute exposure (30 min) to puerarin on vascular relaxation. Rings from porcine coronary artery of either sex were used. The highest concentration of puerarin (100 microM) produced a small but statistically significant relaxation of U46619-contracted rings. Vascular relaxations were also studied in the presence of lower concentrations of puerarin (0.1, 1 and 10 microM) which had no direct relaxation effect. Puerarin enhanced vasorelaxation to endothelium-independent relaxing agents, sodium nitroprusside and cromakalim. However, puerarin had no effect on vasorelaxation induced by endothelium-dependent relaxing agents, bradykinin and calcium ionophore A23187. The potentiating action of puerarin (10 microM) on sodium nitroprusside-mediated relaxation was not affected by the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), or by the disruption of the endothelium with Triton X-100. The effect of puerarin was reversible following a washout period. The potentiating effects were comparable with the 3'-5'-cyclic adenosine monophosphate (cyclic AMP) analogues, 8-bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP; 10 muM) and Sp-isomer [S nomenclature refers to phosphorus] of adenosine-3', 5'-cyclic monophosphorothioate (Sp-cyclic AMPS; 3 microM), but not the 3'-5'-cyclic guanosine monophosphate (cyclic GMP) analogue, 8-bromoguanosine-3'-5'-cyclic monophosphate (8-Br-cyclic GMP; 3 microM). The cyclic AMP antagonist, Rp-isomer [R nomenclature refers to phosphorus] of 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic AMPS; 10 microM), but not cyclic GMP antagonist, Rp-isomer of 8-bromoguanosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic GMPS; 10 microM), reversed the effects of puerarin (10 microM) on the enhancement of vasorelaxation to sodium nitroprusside. Our results demonstrated that puerarin enhanced sodium nitroprusside-induced relaxation, possibly via the cyclic AMP-dependent pathway.
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PMID:Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery. 1702 64

Although the cardioprotective role of carbon monoxide (CO) has been studied against myocardial ischemia-reperfusion (I/R) injury, the role of coronary endothelium and underlying mechanism in carbon monoxide-induced cardioprotection is not well understood in isolated heart. The present study was designed to determine the role of coronary endothelium in CORM-2-mediated cardioprotection during I/R injury in isolated rat heart. Preconditioning with 30microM/l and 50microM/l of CORM-2 for 10min markedly reduced lactate dehydrogenase (LDH) and creatinin kinase (CK) levels in coronary effluent after global ischemia. There was also a significant improvement in coronary flow rate, heart rate, cardiodynamic parameters and marked attenuation in infarct size. However, protective effect was abolished when hearts were pretreated with 100microM CORM-2. We observed that pretreatment with L-NAME (100microM/l), a nitric oxide synthase (NOS) inhibitor did not affect protection by CORM-2 (50microM/l). On the other hand pretreatment with Triton X-100 (0.05% for 20s) to denude endothelium before CORM-2 treatment followed by I/R injury showed similar cardioprotection. Moreover, pretreatment with K(ATP) channel inhibitor, glibenclamide almost completely reversed the cardioprotective effect of CORM-2 in endothelium-denuded hearts. These results indicate that cardioprotection by CORM-2 is highly concentration-dependent, independent of coronary endothelium and cardioprotective effect might be attributed to the activation of K(ATP) channel present on vascular smooth muscle cell (VSMC).
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PMID:Cardioprotective effect with carbon monoxide releasing molecule-2 (CORM-2) in isolated perfused rat heart: Role of coronary endothelium and underlying mechanism. 2039 2

The length-active tension relation or heterometric regulation (Frank-Starling mechanism) is modulated by nitric oxide (NO) which, released in pulsatile fashion from the beating heart, improves myocardial relaxation and diastolic distensibility. The NO signaling is also implicated in the homeometric regulation exerted by extrinsic factors such as autonomic nervous system, endocrine and humoral agents. In the in vitro working frog heart, the Chromogranin A (CGA)-derived peptide, Catestatin (CTS; bovine CGA344-364), exerts a direct cardio-suppressive action through a NOS-NO-cGMP-mediated mechanism which requires the functional integrity of the endocardial endothelium (EE) and its endothelin-1 B type (ETB) receptor. However, functional interplay between NO and CTS and their role in the Frank-Starling response of the frog heart are lacking. Here we show that CTS improves the sensitivity to preload increases similar to that exerted by NO. This effect is abolished by inhibition of NO synthase (L-NAME), guanylate cyclase (ODQ), protein kinase G (KT5823), PI3K (Wortmannin), as well as by the functional damage of EE (Triton X-100) suggesting that CTS operates through an EE-dependent NO release. On the whole, the use of the avascular frog heart revealed the EE as major sensor-transducer interface between the physical (volume load) and chemical (CTS) stimuli, NO functioning as a connector between heterometric and homeometric regulation.
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PMID:Cardiac heterometric response: the interplay between Catestatin and nitric oxide deciphered by the frog heart. 2255 2