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)

In addition to stretch, some hormones and neurotransmitters influence atrial natriuretic factor (ANF) secretion from the mammalian heart. In the present study, we investigated the effect of specific inhibition of nitric oxide/endothelium-derived relaxing factor (NO/ EDRF) on release of ANF from the isolated spontaneously beating heart during basal conditions and in response to arginine vasopressin (AVP; 3 x 10(-8) M), acetylcholine (ACh; 10(-6) M), and angiotensin II (ANG II; 4 x 10(-7) M) to determine whether NO is involved as a mediator of basal and hormone-modulated secretion of ANF. Basal secretion from control hearts remained stable for the duration of the experiment. Intracoronary perfusion of the heart with AVP, ACh, and ANG II reduced ANF secretion significantly by 58 +/- 4, 51 +/- 6, and 26 +/- 8%, respectively, independently of concomitant changes in coronary flow and heart rate. The NO donor sodium nitroprusside (SNP, 10(-4) M) inhibited ANF secretion comparably to AVP and ACh. The effect of SNP was not affected by inhibition of NO synthase activity with NG-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-5) M). Similarly, L-arginine, (3 x 10(-4) M) but not its stereoisomer D-arginine (3 x 10(-4) M), significantly reduced ANF secretion. Subsequent perfusion with AVP singly or in combination with L-arginine or D-arginine did not affect ANF secretion further. The inhibitor of NO synthase NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-5) M) did not affect basal secretion, but prevented the inhibitory effect of AVP and ACh. The effect of ANG II was not changed by L-NMMA. These results indicate that AVP and ACh inhibit ANF secretion in the isolated heart indirectly by stimulating NO/EDRF and suggest a novel function of NO/EDRF as a negative modulator of ANF secretion.
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PMID:Effect of nitric oxide inhibition on secretion of atrial natriuretic factor in isolated rat heart. 876 65

1. In rat aortic rings precontracted with phenylephrine, the beta-adrenoceptor agonist isoprenaline (10 nM to 30 microM) produces greater relaxant effects in preparations with endothelium than in endothelium-denuded preparations. The aim of this study was to determine the mechanisms involved in this effect and in particular investigate the possibility of a synergistic action between adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP). 2. Isoprenaline-induced relaxation of rat aortic rings precontracted with phenylephrine was greatly reduced by the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 300 microM) or the soluble guanylate cyclase inhibitors methylene blue (10 microM) or IH-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) but unaffected by indomethacin (10 microM), a cyclo-oxygenase inhibitor. Similarly, in intact rings, the concentration-response curve of forskolin (10 nM to 1 microM) was shifted to the right upon endothelium removal or treatment with methylene blue. 3. In endothelium-denuded rat aortic rings, isoprenaline-induced relaxation was potentiated by the guanylate cyclase activators atrial natriuretic factor (ANF, 1 to 10 nM) and sodium nitroprusside (SNP, 1 to 10 nM), and to a greater extent in the presence of the cyclic GMP-specific phosphodiesterase (PDE 5) inhibitor, 1,3dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl) pyrazolo [3,4-d] pyrimidin-4-(5H)-one (DMPPO, 30 nM). Relaxation induced by isoprenaline was also potentiated by the cyclic GMP-inhibited PDE (PDE 3) inhibitor cilostamide (100 nM). 4. Intracellular cyclic nucleotide levels were measured either in rat cultured aortic smooth muscle cells or in de-endothelialized aortic rings. In both types of preparation, isoprenaline (5 nM and 10 microM) increased cyclic AMP levels and this effect was potentiated by cilostamide (10 microM), by rolipram, a cyclic AMP-specific PDE (PDE 4) inhibitor (10 microM) and by cyclic GMP-elevating agents (50 nM ANF or 30 nM SNP plus 100 nM DMPPO). In isoprenaline-stimulated conditions, the increase in cyclic AMP induced by rolipram was further potentiated by cilostamide and by cyclic GMP-elevating agents. Cilostamide and cyclic GMP-elevating agents did not potentiate each other, suggesting a similar mechanism of action. 5. We conclude that in vascular smooth muscle (VSM) cells an increase in cyclic GMP levels may inhibit PDE 3 and, thereby, cyclic AMP catabolism. Under physiological conditions of constitutive NO release, and to a greater extent in the presence of the PDE 5 inhibitor DMPPO, cyclic GMP should act synergistically with adenylate cyclase activators to relax VSM.
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PMID:Effects of cyclic GMP elevation on isoprenaline-induced increase in cyclic AMP and relaxation in rat aortic smooth muscle: role of phosphodiesterase 3. 889 66

We investigated the nature of cGMP-synthesizing cells in the developing rat forebrain using cGMP-immunocytochemistry in combination with in vitro incubation of brain slices. When brain slices of immature rats, aged between 1 and 4 weeks, were incubated with sodium nitroprusside (SNP), a nitric oxide (NO) donor compound, in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), small round cells with a few processes in and around the corpus callosum were visualized with the cGMP-antibody. The morphology and the distribution of the cGMP-positive cells were consistent with the criteria for oligodendrocytes. Furthermore, the cGMP-positive cells expressed 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and gelsolin, which are marker proteins for oligodendrocytes. Therefore, we concluded that the cGMP-positive cells were oligodendrocytes. A subpopulation of the oligodendrocyte was found to be cGMP-immunoreactive also when slices were incubated in the absence of SNP. Furthermore, incubation of the slice in the presence of L-NAME, an inhibitor of NO synthase, but in the absence of SNP abolished cGMP immunostaining. In addition, some populations of neurons and astrocytes in restricted brain areas produced cGMP in response to the incubation with SNP as previously reported, whereas both ameboid and ramified microglial cells did not respond to the treatment. Atrial natriuretic peptide, a stimulator of particulate guanylyl cyclase, enhanced cGMP synthesis in astrocytes in some brain regions but not in oligodendrocytes. These findings indicate that oligodendrocytes in the immature rat brain express soluble guanylyl cyclase. No cGMP-positive oligodendrocytes were found in the mature rat brain, suggesting that cGMP may mediate signals related to myelinogenesis in the rat brain.
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PMID:Nitric oxide-mediated cGMP synthesis in oligodendrocytes in the developing rat brain. 909 73

Nitric oxide (NO) plays a crucial role in the regulation of kidney function and metabolism. Our previous study showed that dexamethasone, one of several known selective inhibitors of inducible nitric oxide synthase (NOS), had a stimulatory effect on soluble guanylyl cyclase in the glomeruli of rat kidney. However, in the presence of dexamethasone, the atrial natriuretic factor (ANF)-dependent system remained suppressed. The aim of the present study was to investigate whether inhibition of synthesis of endogenous NO modulates the activity of the guanylyl cyclase system(s) in glomeruli. In these studies, rats were injected with a non-selective NOS inhibitor, N-omega-nitro-L-arginine methyl ester (NAME; NAME-group), or saline solution (controls; C-group). Creatinine clearance (C(Cr)), and plasma and urinary nitrate/nitrite (NOx-) levels decreased in the NAME-group, but plasma and urinary guanosine 3',5'-cyclic monophosphate (cGMP) contents were unchanged. In the presence of 0.1 microM ANF, synthesis of cGMP in the NAME-group exceeded threefold the cGMP production in the C-group. In addition, the pre-contracted glomeruli of the NAME-group were fully relaxed at 0.1 microM ANF, but glomeruli obtained from the C-group were relaxed in the presence of a 10 times higher dose of ANF. The increased sensitivity of glomeruli to ANF was possibly due to the more than doubled activity of particulate guanylyl cyclase (pGC) in the NAME-group in comparison with the C-group. In the presence of 100 microM sodium nitroprusside (SNP), soluble guanylyl cyclase (sGC) generated significantly lower cGMP production in the NAME-group than in the C-group (1.61 +/- 0.33 vs. 2.91 +/- 0.69 nmol/mg protein/10 min, respectively). These results demonstrate that inhibition of the synthesis of endogenous NO may also have an inhibitory effect on the activity of sGC. In addition, increased activity of the pGC and ANF-dependent system appears to be compensatory to the altered activity of soluble guanylyl cyclase.
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PMID:Inhibition of endogenous nitric oxide synthesis activates particulate guanylyl cyclase in the rat renal glomeruli. 929 Nov 84

Inhibition of nitric oxide (NO) synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) increases arterial pressure (PA) and profoundly reduces renal blood flow (RBF). Here we report that L-NAME causes changes in the PA-RBF transfer function which suggest augmentation of the approximately 0.2 Hz autoregulatory mechanism. Attenuation of PA fluctuations from 0.06 to 0.11 Hz was enhanced, indicating increased efficacy of autoregulation. Also, the rate of gain reduction between 0.1 and 0.2 Hz increased while the associated phase peak became > or = pi/2 radians, indicating emergence of a substantial rate-sensitive component in this system so that autoregulatory responses to rapid PA changes become more vigorous. Infusion of L-arginine partly reversed the pressor response to L-NAME, but not the renal vasoconstriction or the changes in the transfer function. The ability of atrial natriuretic factor (ANF), which also acts via cGMP, to replace NO was assessed. ANF dose dependently reversed but did not prevent the pressor response to L-NAME, indicating additive responses. ANF did not restore RBF or reverse the changes in the transfer function induced by L-NAME. The rate-sensitive component that was enhanced by L-NAME remained prominent, suggesting that either ANF did not adequately replace cGMP or provision of a basal level of cGMP was not able to replace cGMP generated in response to NO. It is concluded that NO synthase inhibition changes RBF dynamics with the most notable change being increased contribution by a rate-sensitive component of the myogenic system.
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PMID:Nitric oxide, atrial natriuretic factor, and dynamic renal autoregulation. 1058 82

Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microg x min(-1), sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 +/- 0.3 mL x 100 g(-1) body wt. (n = 7) vs. D-NAME, 6.8 +/- 0.2 mL x 100 g(-1) body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 +/- 0.1 mL x 100 g(-1) body wt. (n = 6) vs. D-NAME, 4.8 +/- 0.2 mL x 100 g(-1) body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did decrease plasma ET levels in the pregnant rats [L-NAME, 19.6 +/- 1.6 pg x mL(-1) (n = 8) vs. D-NAME, 11.6 +/- 2.5 pg x mL(-1) (n = 9); P < 0.05]. Our results confirm that NO is involved in cardiovascular homeostasis in pregnancy; NOS inhibition selectively reduces plasma volume in pregnant rats, thus mimicking a major pathophysiological perturbation of preeclampsia. However, it does not induce the hormonal changes characteristic of preeclampsia, namely the decrease in PRA and increase in plasma ET and ANF levels.
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PMID:Effect of nitric oxide synthase inhibition on cardiovascular and hormonal regulation during pregnancy in the rat. 1084 38

Antioxidants and antioxidant enzymes are known to protect against cell death induced by reactive oxygen species. However, apart from directly quenching free radicals, little is known about the effect of antioxidants on hormone-activated second messenger systems. We previously found that antioxidants such as 17-beta estradiol and resveratrol activate membrane-bound guanylate cyclase GC-A, the receptor for atrial natriuretic factor (ANF), in PC12 cells. It is possible that other antioxidants may also activate membrane-bound guanylate cyclase GC-A. The aim of this study was to determine if dithiothreitol (DTT), vitamin C, and vitamin E activate membrane-bound guanylate cyclase GC-A in PC12 cells. The results showed that both DTT and vitamin C increased cGMP levels in PC12 cells, whereas vitamin E had no effect. DTT and vitamin C inhibited membrane-bound guanylate cyclase activity stimulated by ANF in PC12 cells. In contrast, DTT and vitamin C had no effect on soluble guanylate cyclase activity stimulated by substance P. Furthermore, NO synthase inhibitors L-NAME and aminoguanidine did not affect DTT- and vitamin C-stimulated guanylate cyclase activity. The results indicate that DTT and vitamin C, but not vitamin E, activate membrane-bound guanylate cyclase GC-A in PC12 cells.
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PMID:Antioxidants, vitamin C and dithiothreitol, activate membrane-bound guanylate cyclase in PC12 cells. 1127 22

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.
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PMID:Impaired response to insulin associated with protein kinase C in chronic fructose-induced hypertension. 1252 77

Despite a variety of biological roles for nitric oxide (NO) in the cardiovascular system, little is known about whether NO is involved in cardiac hypertrophy. We hypothesized that NO production following a sustained increase in shear stress by volume-overload modifies the level of cardiac hypertrophy independent of hemodynamic changes. Volume-overload was induced by shunt formation between the left common carotid artery and the external jugular vein in 21 rabbits. These shunt rabbits were randomly assigned to 3 groups: shunt with no treatment (n = 8), shunt treated with a low dose of N(G)-nitro-L-arginine methyl ester (L-NAME. 0.5 g/L in drinking water, n=8), and shunt with a high dose of L-NAME (1.5 g/L, n = 5). Eight sham operated rabbits were used as controls. Treatments were started immediately after operation and were continued for 6 weeks. Chronic volume-overload by shunt formation caused left ventricular dilatation and arterial enlargement proximal to the fistula. The relative wall thickness of the left ventricle was decreased, indicating eccentric cardiac hypertrophy. L-NAME elevated mean arterial blood pressure (P < 0.01) and reduced the increment of cardiac output (P < 0.05). L-NAME attenuated ventricular weight (P < 0.01) ventricular cavity dilatation (P < 0.01). and arterial enlargement (P < 0.05). The re-capitulation of atrial natriuretic factor mRNA in the hypertrophied left ventricular myocardium by volume-overload was attenuated with L-NAME. In this model with chronic volume-overload, NO plays a pivotal role in the progression of cardiovascular remodeling by regulating the loading conditions of the heart.
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PMID:Role of nitric oxide in the progression of cardiovascular remodeling induced by carotid arterio-venous shunt in rabbits. 1262 44

Although studies have suggested a role for angiogenesis in determining heart size during conditions demanding enhanced cardiac performance, the role of EC mass in determining the normal organ size is poorly understood. To explore the relationship between cardiac vasculature and normal heart size, we generated a transgenic mouse with a regulatable expression of the secreted angiogenic growth factor PR39 in cardiomyocytes. A significant change in adult mouse EC mass was apparent by 3 weeks following PR39 induction. Heart weight; cardiomyocyte size; vascular density normalization; upregulation of hypertrophy markers including atrial natriuretic factor, beta-MHC, and GATA4; and activation of the Akt and MAP kinase pathways were observed at 6 weeks post-induction. Treatment of PR39-induced mice with the eNOS inhibitor L-NAME in the last 3 weeks of a 6-week stimulation period resulted in a significant suppression of heart growth and a reduction in hypertrophic marker expression. Injection of PR39 or another angiogenic growth factor, VEGF-B, into murine hearts during myocardial infarction led to induction of myocardial hypertrophy and restoration of myocardial function. Thus stimulation of vascular growth in normal adult mouse hearts leads to an increase in cardiac mass.
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PMID:Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice. 1797 62


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