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

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Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of bradykinin (BK) on endothelin-1 (ET-1)-induced vasoconstriction and its mechanism were investigated. The development of isometric force of arterial rings of canine coronary, renal and femoral arteries was recorded using a organ bath containing Krebs-Henseleit buffer aerated with 95% O2 and 5% CO2. ET-1 at more than 10(-9) M dose-dependently induced vascular contraction similarly among the three arteries. BK at more than 10(-8) M dose-dependently suppressed the ET-1-induced vasoconstriction only in the presence of endothelium, and the effect of BK was largest in the coronary arteries. The BK-induced suppression was not affected by addition of des-Arg9-[Leu8]-BK, an antagonist for B1-receptor, but did be completely reversed by addition of B2-receptor antagonist (10(-6) M) [D-Arg0,Hyp3,Thi5,8,D-Phe7]-BK. The BK's suppression of the ET-1-induced vasoconstriction was partly reversed by additions of each 10(-5) of Ng-nitro-L-arginine, a substrate inhibitor of nitric oxide, methylene blue, an inhibitor of soluble guanylate cyclase, or indomethacin, an inhibitor of cyclooxygenase. The reversing effects of methylene blue and indomethacin were additive. BK suppresses the ET-1-induced vasoconstriction through B2-receptor on the endothelium. Both endothelial nitric oxide and prostaglandin(s) are participated in the BK's effect.
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PMID:Bradykinin suppresses endothelin-induced contraction of coronary, renal and femoral arteries through its B2-receptor on the endothelium. 133 47

We have examined the mechanism governing guanosine 3',5'-cyclic monophosphate (cGMP)-associated photoinduced relaxation elicited by long-wavelength ultraviolet (UV) light of endothelium-removed, isolated bovine pulmonary arteries. Hypoxia, produced by gassing of the organ bath solution with 95% N2-5% CO2, inhibited photorelaxation. Photorelaxation was also inhibited by cyanide (1 mM NaCN) but was potentiated by lactate (5 mM). Irradiation of bovine pulmonary arterial smooth muscle with UV light (or exposure to exogenous H2O2) stimulated cyanide-inhibitable oxidation of methanol to formaldehyde, suggesting that UV light increased H2O2 metabolism via catalase. The UV light-induced oxidation of methanol by pulmonary arterial smooth muscle was also inhibited by hypoxia. Consumption of O2 was detected when pulmonary arterial tissue was exposed to UV light, but cyanide failed to interfere with this effect, consistent with the photochemical reduction of O2 within vascular smooth muscle in a manner independent of mitochondrial respiration. We propose that photorelaxation is associated with the intracellular photochemical reduction of O2 to form H2O2, which elicits increases of vascular smooth muscle cGMP levels via the catalase-dependent activation of soluble guanylate cyclase. In addition, we hypothesize that the photooxidation of NAD(P)H could contribute to the generation of H2O2, since the enhancement of photorelaxation by lactate may originate from increased levels of NADH.
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PMID:Association of pulmonary artery photorelaxation with H2O2 metabolism by catalase. 192 95

We have reported evidence that endothelium-independent relaxations of isolated bovine pulmonary arteries to H2O2 and to reoxygenation with 95% O2-5% CO2 after brief exposure to N2 (5% CO2) appear to be mediated by the activation of guanylate cyclase via H2O2 metabolism through catalase. Treatment of endothelium-removed pulmonary arteries with a potential guanylate cyclase-inhibitor, LY 83583, or with the inhibitor of the Zn+2, Cu+2-superoxide dismutase (SOD) diethyldithiocarbamic acid (DETCA), antagonized guanosine 3',5'-cyclic monophosphate (cGMP)-associated relaxation to H2O2, to reoxygenation and to glyceryl trinitrate, but not the adenosine 3',5'-cyclic monophosphate-associated relaxation to isoproterenol. Superoxide anion (O2-.) levels, detected by lucigenin-elicited chemiluminescence, were enhanced by LY 83583 or DETCA treatment of pulmonary arteries at ambient PO2. Chemiluminescence produced by LY 83583 was markedly potentiated by DETCA treatment, decreased at addition of exogenous SOD, and inhibited markedly by anoxia. LY 83583, but not DETCA, stimulated cyanide-insensitive O2 consumption, consistent with redox cycling of the compound independent of mitochondrial respiration. We propose that O2-. generated on the metabolism of LY 83583, or from cellular electron donors after SOD inhibition by DETCA, inhibits cGMP-mediated relaxations of pulmonary arteries.
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PMID:Superoxide anion inhibits cGMP-associated bovine pulmonary arterial relaxation. 217 63

The distribution of cyclic guanosine 3',5' monophosphate (cGMP) producing cells in various organs of the rat were studied immunocytochemically using antibodies raised against formaldehyde-fixed cGMP. Sodium nitroprusside (SNP), a direct activator of guanylate cyclase and vasodilator, was used to enhance cGMP levels. In order to reach all organs optimally, whole body perfusion was performed using a modified Krebs-Ringer buffer at 37 degrees C, aerated with 5% CO2/95% O2, also containing isobutyl methyl xanthine (IBMX); a phosphodiesterase inhibitor. After 15-min pre-perfusion, SNP was added to the perfusate, followed by fast fixation with ice-cold 4% paraformaldehyde-phosphate buffer. After vehicle perfusion, only the retina showed cGMP immunoreactivity in the photoreceptor and ganglion layer, while other organs lacked cGMP immunoreactivity. After 15-min perfusion with SNP (10 microM), enhanced cGMP immunostaining was seen in smooth muscles of the aorta, amacrine-like cells in the retina, glomeruli of the kidney cortex, blood vessels in the dura mater, as well as cells in the pineal and in the median eminence. The results indicate that the distribution and the reactivity of cGMP producing cells, situated outside the blood brain barrier, can be studied by immunocytochemistry after pharmacological manipulations of the intact tissue with a nitrovasodilator using whole body perfusion.
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PMID:cGMP immunocytochemistry in aorta, kidney, retina and brain tissues of the rat after perfusion with nitroprusside. 255 68

Several studies on the effects of atrial natriuretic polypeptide (ANP) on aldosterone production using isolated adrenal cells have been reported, and they have consistently demonstrated the reduced production of aldosterone by ANP. However, the results on the corticosterone production are sundry. Since ANP selectively activates particulate guanylate cyclase, a possibility could exist that cyclic GMP is the second messenger of ANP signal transduction. In order to demonstrate unequivocally a correlation of cyclic nucleotide levels with the ANP-induced steroidogenesis, we investigated the effects of various concentrations of alpha-human atrial natriuretic polypeptide (alpha-hANP) on aldosterone, corticosterone, cyclic AMP and cyclic GMP production in isolated glomerulosa and fasciculata cells of the rats. Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male Wistar rats. The cell pellet was suspended in Hanks balanced salt solution-0.1% BSA buffer and distributed in 900 microliter aliquots to 12 X 75 mm glass tubes. The samples were preincubated for 90 min. in a 37 degrees C water bath under an atmosphere of 5% CO2/95% O2. Aliquots of the test samples were added in a 100 microliter volume and incubated for 4 hr. Total volume of the incubation mixture is 1.0 ml. Aldosterone, cyclic AMP and cyclic GMP were measured by radioimmunoassay and corticosterone was determined by fluorimetric method. The results indicated that alpha-hANP inhibited the secretion of aldosterone and corticosterone in rat glomerulosa cells. Alpha-hANP significantly decreased cyclic AMP production in the rat glomerulosa cells, while it markedly stimulated cyclic GMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Stimulated corticosterone production by alpha-human atrial natriuretic polypeptide with increased cyclic GMP production]. 282 46

1. The vasodilator effects of hydralazine in vitro, using the Krebs' perfused human placental lobule was studied. Single placental lobules were bilaterally perfused (maternal and fetal sides 5 mL/min each, 95% O2, 5% CO2, 37 degrees C) and changes in fetal arterial pressure (FAP) and venous outflow (VO) were recorded. 2. Submaximal vasoconstriction was induced by KCl (20-50 mmol/L), which increased basal FAP from 22.8 +/- 1.7 to 91.3 +/- 3.9 mmHg (n = 9, P < 0.001), and decreased VO from 4.1 +/- 0.6 to 0.2 +/- 0.1 mL/min (n = 6, P < 0.01). 3. Hydralazine caused vasodilatation (IC50 1.9 mmol/L, n = 9) and increased VO in the presence of KCl-induced vasoconstriction. 4. Infusion of N omega-nitro-L-arginine (100 mumol/L) to block nitric oxide synthase caused the basal FAP to increase from 30.9 +/- 5.9 to 47.4 +/- 6.7 (n = 6, P < 0.05) and significantly potentiated hydralazine-induced vasodilatation (n = 7, P < 0.05). 5. The soluble guanylate cyclase inhibitor LY 83583 (6-anilino-5,8-quinolinedione) (1 mumol/L) significantly antagonized the vasodilatation produced by hydralazine (n = 5, P < 0.05). 6. Thus, Hydralazine appears to activate guanylate cyclase, leading to increased cyclic GMP in fetal arterial vascular smooth muscle to cause vasorelaxation. No evidence was obtained to suggest that hydralazine exerted its action by either releasing nitric oxide from endothelial cells in the placenta or acting as a nitric oxide donor.
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PMID:Effect of inhibition of nitric oxide synthase and guanylate cyclase on hydralazine-induced vasodilatation of the human fetal placental circulation. 752 52

The relaxant effect of hypercapnia (15% CO2) was studied in isolated circular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro-L-arginine (L-NOARG) and the cytosolic guanylate cyclase inhibitor methylene blue (MB), significantly reduced this relaxation by 54% and 70%, respectively. The effect of L-NOARG was completely reversed by L-arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response to hypercapnia. L-NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 M HCl resulted in relaxation identical to that obtained by lowering the pH with 15% CO2. In vessel segments in which the endothelium had been removed beforehand 15% CO2 induced relaxation that was not different from that seen in vessels with intact endothelium. L-NOARG had no affect in endothelium denuded vessels. The results suggest that high CO2 elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall.
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PMID:Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production. 753 5

Endothelium-intact rat aortic rings were incubated with palytoxin (PTX, 10(-11)-10(-9)M, 10 min) in oxygenated (O2 95%, CO2 5%) baths. Phenylephrine (PE)-contracted vascular rings demonstrated decreasing relaxation to acetylcholine (ACh), depending upon PTX incubation in a dose-dependent manner; however, sodium nitroprusside (NaNP) persisted in returning the ring to its pre-PE tension. After incubation with PTX, relaxation to the receptor-independent, endothelium-dependent relaxant A23187 was also attenuated. Thus, endothelium-dependent mechanism(s) normally responsive to both ACh and A23187, stimulators of nitric oxide (NO) release, were disrupted. Following incubation with PTX, endothelium-independent relaxation to NaNP remained intact but relaxation to atriopeptin II (APII) decreased. Electron microscopy demonstrated microvesiculation of endothelial cell cytoplasm and an irregular luminal surface following incubation with PTX. The intact response to NaNP, despite the loss of relaxation to ACh, indicated that soluble guanylate cyclase was not affected by PTX. However, loss of relaxation to AP-II, involving particulate guanylate cyclase of vascular smooth muscle (VSM), was inhibited by PTX pre-incubation. Determination of the site(s) of action of PTX requires further study.
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PMID:Effect of palytoxin on endothelium-dependent and -independent relaxation in rat aortic rings. 774 26

All-trans retinoic acid (tretinoin) is a known inducer of differentiation of the human monoblastic cell line, U-937. We now report that the ability of retinoic acid (RA) to induce differentiation of U-937 cells into cells possessing respiratory burst activity is enhanced by the known nitric oxide-donating drugs glyceryl trinitrate, molsidomine and CAS 936, and by tetranitromethane in combination with cysteine. RA alone was a strong inducer of U-937 differentiation as indicated by the following responses to 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation: (1) increase in the percentage of cells staining with nitroblue tetrazolium (NBT); (2) increase in the total amount of formazan (the product of NBT reduction by O2-.) as determined spectrophotometrically; (3) increase in hexose monophosphate shunt (HMPS) activity as assessed by [14C]CO2 released from D-[1-14C]glucose. RA was also able to increase mRNA levels for two respiratory burst-related genes and for glucose-6-phosphate dehydrogenase (G6PD), an HMPS enzyme. Other indications of differentiation were reduced cell proliferation, increased adherence and altered nuclear morphology. The observed increase in formazan production and HMPS activity and the reduction of cell proliferation due to RA were augmented by co-treatment with either glyceryl trinitrate, molsidomine, CAS 936 or tetranitromethane plus cysteine. Glyceryl trinitrate alone increased HMPS activity and G6PD mRNA levels and also reduced cell proliferation. Glyceryl trinitrate, molsidomine and CAS 936 are presumed to release nitric oxide and increase intracellular cGMP levels by stimulation of soluble guanylate cyclase. The mechanism of action of tetranitromethane is less certain, although it may also generate reactive nitrogen intermediates. These data suggest that a NO./cGMP pathway may augment a retinoic acid-mediated pathway to enhance maturation of U-937 cells with respect to the respiratory burst. Glyceryl trinitrate may act additionally by another pathway.
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PMID:Potentiation of retinoic acid-induced U-937 differentiation into respiratory burst-competent cells by nitric oxide donors. 776 33

The effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of soluble guanylate cyclase; glybenclamide, a ATP-sensitive K+ channel blocking agent; and 5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl)-[1,1']-biphenyl-4- yl]methyl]-3H-imidazo[4,5-b]pyridine (L158809), an angiotensin II type I receptor antagonist, on the response to ventilatory hypoxia were investigated in the isolated blood-perfused rat lung. Under conditions of controlled pulmonary blood flow, and constant left atrial pressure, injections of glybenclamide into the pulmonary arterial perfusion circuit significantly increased baseline pulmonary arterial perfusion pressure, whereas administration of N omega-nitro-L-arginine methyl ester produced smaller increases in baseline tone. Ventilatory hypoxia (3% O2-5% CO2-92% N2) significantly increased pulmonary arterial perfusion pressure and the response was reproducible with respect to time. Following administration of N omega-nitro-L-arginine methyl ester or LY83583, the response to hypoxia was significantly increased, whereas the response to hypoxia was not changed by glybenclamide or atropine. N omega-Nitro-L-arginine methyl ester also significantly enhanced pressor responses to angiotensin II, but had no effect on the pressor response to serotonin. When pulmonary vascular tone was increased with hypoxia, vasodilator responses to acetylcholine were inhibited by N omega-nitro-L-arginine methyl ester and vasodilator responses to levcromakalim were reduced by glybenclamide. In addition, L158809 did not alter the pressor response to hypoxia, whereas responses to angiotensin II were reduced in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of N omega-nitro-L-arginine methyl ester, LY83583, glybenclamide and L158809 on pulmonary circulation. 782 44


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