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 effects of hexasulfobutylated C(60) (FC(4)S) and monomalonic acid C(60) (MMA C(60)), the fullerene C(60) derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C(60) (10 micromol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C(60) (10 micromol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC(4)S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC(4)S (10 micromol/l). In the denuded aortic rings, FC(4)S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC(4)S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 micromol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC(4)S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.
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PMID:Effect of hexasulfobutylated C(60) on the isolated aortic ring of guinea pig. 1180 49

1. Broilers were divided at 42 to 44 d of age into a Control group (n=30) and a Treatment group (n=30). The mean pulmonary arterial pressure (mPAP) and electrocardiogram (ECG) leads II and aV(F) were measured 1, 2 and 4 h after an intravenous injection of 0.9% saline (Control group) or Nomega-nitro-L-arginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase and thus an inhibitor of endothelial nitric oxide (NO) production (Treatment group). 2. At 1 and 2 h but not 4 h post-injection, L-NAME significantly increased the mPAP and the amplitudes of the ECG S-wave and RS-wave leads II and aVF when compared with Control values. 3. The correlation coefficients between the mPAP and the ECG S-wave and RS-wave amplitudes for lead II within the Treatment group were -0.848 and -0.553 at 1 h and -0.798 and -0.512 at 2 h, respectively. The corresponding coefficients for lead aVF were -0.735, -0.596, -0.663 and -0.724, respectively. 4. After suitable mPAP and ECG values had been recorded at each time interval, sodium nitroprusside (SNP), which acts as a short-lived NO donor molecule, was injected intravenously via a right-cardiac catheter. Within 5 min after the SNP injection, the mPAP and the ECG lead II S-wave and RS-wave amplitudes were transiently reduced to levels that, at 1 and 2 h after L-NAME injection, did not differ from Control values. Within 10 min after the SNP injection, all values returned to the levels previously induced by L-NAME. 5. These results demonstrate that L-NAME increased the myocardial contractility and PAP, whereas SNP transiently reversed the effects of L-NAME on myocardial contractility and PAP. It appears likely from these results that the pulmonary vascular endothelium releases NO that in turn reduces the pulmonary vascular resistance or attenuates myocardial contractility in broiler chickens.
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PMID:Pulmonary arterial pressure and electrocardiograms in broiler chickens infused intravenously with L-NAME, an inhibitor of nitric oxide synthase, or sodium nitroprusside (SNP), a nitric oxide donor. 1204 97

Low-density lipoprotein (LDL) and its oxidized derivatives are hypothesized to impair vascular function by increasing superoxide anion (O.). To investigate mechanisms in situ, isolated carotid arteries were incubated with native LDL (nLDL) or minimally oxidized LDL (mmLDL). With the use of en face fluorescent confocal microscopy and hydroethidine, an oxidant-sensitive fluorescent probe, we found that nLDL increased O. in vascular endothelium greater than fourfold by an N(omega)-nitro-L-arginine methyl ester (L-NAME)-inhibitable mechanism. In contrast, mmLDL increased O. in vascular endothelium greater than eightfold by mechanisms that were partially inhibited by L-NAME and allopurinol and essentially ablated by diphenyleneiodium. These data indicate that both nLDL and mmLDL uncouple endothelial nitric oxide synthase (eNOS) activity and that mmLDL also activates xanthine oxidase and NADPH oxidoreductase to induce greater increases in O. generation than nLDL. Western analysis revealed that both lipoproteins inhibited A-23187-stimulated association of heat shock protein 90 (HSP90) with eNOS without inhibiting phosphorylation of eNOS at serine-1179 (phospho-eNOS), an immunological index of electron flow through the enzyme. As HSP90 mediates the balance of.NO and O. generation by eNOS, these data provide new insight into the mechanisms by which oxidative stress, induced by nLDL and mmLDL, uncouple eNOS activity to increase endothelial O. generation.
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PMID:Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ. 1212 24

The function of endoplasmic reticulum in hypertensive vascular endothelium has not been intensively studied. The current study was designed to investigate a role of intracellular Ca2+ stores in endothelium-dependent relaxations to acetylcholine using femoral arteries obtained from Wistar-Kyoto (WKYs) and spontaneously hypertensive rats (SHRs). Rings were prepared from the femoral arteries and changes in isometric tension were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with serotonin were identical in WKYs and SHRs. Cyclopiazonic acid (CPA) inhibited the relaxation in SHRs but not in WKYs. In WKYs, acetylcholine evoked smaller relaxations in rings contracted with KCl than in those contracted with serotonin, whereas in SHRs the relaxation was not affected by the contractile agonists used. The relaxation in rings contracted with KCl was abolished by Nw-nitro-l-arginine methyl ester (l-NAME) and was reduced by CPA to a similar extent in both strains. In rings contracted with serotonin, l-NAME abolished the relaxation in SHRs, but the inhibitor only partially reduced the relaxation in WKYs. CPA did not alter the relaxation in the presence of l-NAME. Endothelium-independent relaxations to sodium nitroprusside were not affected by CPA. These results suggest that acetylcholine relaxes rat femoral arteries by releasing both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). In SHRs, the relaxation is preserved, but the release of EDHF is absent. CPA inhibits the relaxation mediated by nitric oxide, but not EDHF and, thus, inhibits the relaxation in SHRs but not in WKYs. Functional alteration of endoplasmic reticulum in the hypertensive endothelium cannot be detected.
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PMID:Altered effect of cyclopiazonic acid on endothelium-dependent relaxation in femoral arteries from hypertensive rats. 1213 51

The aim of the present study was to investigate the effects of Xp(5)X and Xp(6)X (X = guanosine (G) or adenosine (A); n = 5 and 6), which have been identified in human platelets, on coronary vascular tone. The activation of purinoceptors in rat coronary vasculature by Xp(5)X and Xp(6)X was evaluated by measuring their effects on perfusion pressure in the Langendorff perfused rat. Ap(5)X and Ap(6)X induced dose-dependent vasodilation that was due to P2Y(1) receptor activation, as evidenced by use of the selective P2Y(1) receptor antagonist 2'-deoxy-N(6)-methyl-adenosine 3',5'-diphosphate diammonium (MRS2179). Vasodilation was induced by NO release, as evidenced by inhibition of nitric oxide synthases (NO synthases) by N(G)-nitro-L-arginine methyl ester (L-NAME). The dose-dependent decrease in coronary perfusion pressure induced by Ap(5)X and Ap(6)X was converted to a dose-dependent increase in perfusion pressure after inhibition of NO synthases by L-NAME. After endothelium removal, the vasodilation elicited by Ap(5)X and Ap(6)X was converted to a vasoconstriction which could be inhibited by P2X receptor blockade. Ap(5)A, Ap(5)G, Ap(6)A and Ap(6)G are vasodilating or vasoconstricting nucleotides that activate P2Y(1) or P2X receptors depending on the status of the coronary vascular endothelium.
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PMID:Effects of dinucleoside polyphosphates on regulation of coronary vascular tone. 1214 43

1. A possible role of nitric oxide (NO) as a modulator of capsaicin-sensitive sensory neurotransmission in blood vessels was investigated in the rat isolated mesenteric arterial bed. 2. Electrical field stimulation (EFS) of methoxamine-preconstricted mesenteric beds elicited frequency-dependent vasorelaxation mediated by capsaicin-sensitive sensory nerves. N(G)-nitro-L-arginine methyl ester (L-NAME, 10 and 300 microM) and 7-nitroindazole (7-NI, 100 microM), inhibitors of nitric oxide synthase (NOS), augmented sensory neurogenic vasorelaxation. D-NAME (300 microM), 6-aminoindazole (100 microM) and N(omega)-propyl-L-arginine (50 nM), a selective inhibitor of neuronal NOS, were without effect. The effect of 10 microM L-NAME was reversed by L-arginine (1 mM), the substrate for NOS. 3. L-NAME (300 microM) and 7-NI (100 microM) had no significant effect on vasorelaxations to calcitonin gene-related peptide (CGRP), the principal motor neurotransmitter of capsaicin-sensitive sensory nerves in rat mesenteric arteries, or to capsaicin, indicating a prejunctional action. The inhibitors of NOS had no effect on vasorelaxation to forskolin, but augmented vasorelaxation to sodium nitroprusside (SNP). 4. Removal of the endothelium augmented sensory neurogenic vasorelaxation, but did not affect vasorelaxation to CGRP, indicating a prejunctional action of endothelial NO. 5. In the absence of endothelium, L-NAME (300 microM) inhibited, and 7-NI (100 microM) caused no further augmentation of sensory neurotransmission. 6. SNP (100 nM), a nitric oxide donor, attenuated sensory neurogenic relaxations to EFS. 7. In rat isolated thoracic aortic rings, L-NAME (100 microM) and 7-NI (100 microM) attenuated concentration-dependent relaxations to acetylcholine. 8. These data show that NO modulates sensory neurotransmission evoked by EFS of the rat isolated mesenteric arterial bed, and that when NO synthesis is blocked sensory neurogenic relaxation is augmented. The source of NO is the vascular endothelium.
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PMID:Endothelial nitric oxide modulates perivascular sensory neurotransmission in the rat isolated mesenteric arterial bed. 1218 27

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 +/- 0.8 ml (100 ml tissue)(-1) min(-1) at rest to 124 +/- 19, 245 +/- 24, 329 +/- 24 and 312 +/- 25 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 +/- 0.5 ml (100 ml tissue)(-1) min(-1) at rest, and 100 +/- 13, 163 +/- 21, 217 +/- 23 and 256 +/- 28 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively (P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.
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PMID:Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise. 1220

The acute cardiovascular effects of rotundifolone (ROT), the major constituent (63.5 %) of the essential oil of Mentha x villosa (OEMV), were tested in rats by using a combined (in vivo and in vitro) approach. ROT (1, 5, 10, 20 and 30 mg kg(-1) i. v.) induced a significant and dose-dependent hypotension and bradycardia in non-anaesthetized normotensive rats. The hypotensive effect was significantly attenuated by pre-treatment of the rats with atropine (2 mg kg(-1) i. v.) or L-NAME (20 mg kg(-1) i. v.). Furthermore, the bradycardic effect was abolished by atropine. In isolated rat atrial preparations, ROT (10, 100, 300 and 500 microg ml(-1)) produced concentration-related negative inotropic and chronotropic effects. In isolated intact aortic rings, increasing concentractions of ROT (0.3, 1, 10, 100, 300 and 500 microg ml(-1)) were able to antagonize the contractile effect of phenylephrine (1 microM) (IC50 = 184 +/- 6 microg ml(-1)). The smooth muscle-relaxant activity of ROT was inhibited by either removal of vascular endothelium, atropine (1 microM), L-NAME (100 and 300 microM) or indomethacin (10 microM) (IC50 values = 235 +/- 7, 247 +/- 8, 387 +/- 21, 723 +/- 75 and 573 +/- 38 microg ml(-1), respectively). These results suggest that rotundifolone markedly lowers arterial pressure and heart rate in non-anaesthetized animals. The hypotensive action of rotundifolone can be a consequence of a decrease in heart rate and peripheral vascular resistance, probably due to a non-selective muscarinic receptor stimulation.
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PMID:Muscarinic agonist properties involved in the hypotensive and vasorelaxant responses of rotundifolone in rats. 1222 91

Ischemic preconditioning (IPC) may protect the liver from ischemia reperfusion injury by nitric oxide formation. This study has investigated the effect of ischemic preconditioning on hepatic microcirculation (HM), and the relationship between nitric oxide metabolism and HM in preconditioning. Rats were allocated to 5 groups: 1. sham laparotomy; 2. 45 minutes lobar ischemia followed by 2-hour reperfusion (IR); 3. IPC with 5 minutes ischemia and 10 minutes reperfusion before IR; 4. L-arginine before IR; and 5. L-NAME + IPC before IR. HM was monitored by laser Doppler flowmeter. Liver transaminases, adenosine triphosphate, nitrites + nitrates, and guanosine 3'5'-cyclic monophosphate (cGMP) were measured. Nitric oxide synthase (NOS) distribution was studied using nicotinamide adeninine dinucleotide phosphate (NADPH) diaphorase histochemistry. At the end of reperfusion phase, in the IR group, flow in the HM recovered partially to 25.8% of baseline (P < .05 versus sham), whereas IPC improved HM to 49.5% of baseline (P < .01 versus IR). With L-arginine treatment, HM was 31.6% of baseline (NS versus IR), showing no attenuation of liver injury. In the preconditioned group treated with L-NAME, HM declined to 10.2% of baseline, suggesting not only a blockade of the preconditioning effect, but also an exacerbated liver injury. Hepatocellular injury was reduced by IPC, and L-arginine and was increased by NO inhibition with L-NAME. IPC also increased nitrate + nitrate (NOx) and cGMP concentrations. NOS detected by NADPH diaphorase staining was associated with hepatocytes and vascular endothelium, and was induced by IPC. IPC induced NOS and attenuated HM impairment and hepatocellular injury. These data strongly suggest a role for nitric oxide in IPC.
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PMID:Effect of ischemic preconditioning on hepatic microcirculation and function in a rat model of ischemia reperfusion injury. 1247 59

We have previously demonstrated that stimulation of the angiotensin (Ang) II type 2 receptor in vascular smooth muscle cells caused bradykinin production by activating kininogenase in transgenic mice. The aim of this study was to determine whether overexpression of AT2 receptors in cardiomyocytes attenuates Ang II-induced cardiomyocyte hypertrophy or interstitial fibrosis through a kinin/nitric oxide (NO)-dependent mechanism in mice. Ang II (1.4 mg/kg per day) or vehicle was subcutaneously infused into transgenic mice and wild-type mice for 14 days. The amount of cardiac AT2 receptor relative to AT1 receptor in transgenic mice was 22% to 37%. Ang II caused similar elevations in systolic blood pressure (by approximately 45 mm Hg) in transgenic mice and wild-type mice. Myocyte hypertrophy assessed by an increase in myocyte cross-sectional area, left ventricular mass, and atrial natriuretic peptide mRNA levels were similar in transgenic and wild-type mice. Ang II induced prominent perivascular fibrosis of the intramuscular coronary arteries, the extent of which was significantly less in transgenic mice than in wild-type mice. Inhibition of perivascular fibrosis in transgenic mice was abolished by cotreatment with HOE140, a bradykinin B2 receptor antagonist, or L-NAME, an inhibitor of NO synthase. Cardiac kininogenase activity was markedly increased (approximately 2.6-fold, P<0.001) after Ang II infusion in transgenic mice but not in wild-type mice. Immunohistochemistry indicated that both bradykinin B2 receptors and endothelial NO synthase were expressed in the vascular endothelium, whereas only B2 receptors were present in fibroblasts. These results suggest that stimulation of AT2 receptors present in cardiomyocytes attenuates perivascular fibrosis by a kinin/NO-dependent mechanism. However, the effect on the development of cardiomyocyte hypertrophy was not detected in this experimental setting.
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PMID:Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis. 1251 37


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