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At least 19 recordsLinked to original sources

PubMed1998

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2.

Nitric oxide is synthesized in experimental immune complex glomerulonephritis due to local induction of type 2 nitric oxide synthase (NOS2). To determine the role of NOS2, the course of accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM) was examined in mice homozygous for disruption of the NOS2 gene compared with heterozygous littermates. Disease in the wild type strain (129Sv) was characterized by heavy albuminuria, glomerular neutrophil and macrophage infiltration and glomerular thrombosis. NOS2, interleukin 1B (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) mRNA were induced by 24 hours. The NOS2-deficient mutant mice and the heterozygous mice displayed early (24 hr) and full autologous phase (day 6) injury indistinguishable from the wild-type mice. The equivalent degree of albuminuria and glomerular inflammation indicates that NOS2 does not play an essential role in this form of glomerulonephritis in the mouse.

Animals↗

PubMed1997

Clinical and serologic manifestations of autoimmune disease in MRL-lpr/lpr mice lacking nitric oxide synthase type 2.

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl-arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL-lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL-lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL-lpr/lpr mice to the N4 generation. MRL-lpr/lpr littermates homozygous for disrupted NOS2 (-/-), heterozygous for disrupted NOS2 (+/-), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (-/-) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/-) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (-/-) animals, whereas that of (+/+) was high and (+/-) intermediate. The (-/-) mice developed glomerular and synovial pathology similar to that of the (+/-) and (+/+) mice. However, (-/-) mice and (+/-) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (-/-) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

Animals↗

PubMed1999

Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria.

Nitric oxide (NO) plays an important role in host resistance to infection with a variety of organisms. Two recent reports from Gabon and Gambia identified associations of malaria disease severity with the inducible NO synthase (NOS2) promoter G-954C and short allele (<11 repeats) pentanucleotide microsatellite polymorphisms, respectively. It was postulated that there would be a correlation of these polymorphisms with malaria disease severity and with measures of NO production in our cohort of Tanzanian children with malaria. In Tanzanian children, 15% were heterozygous or homozygous for the G-954C polymorphism, and 13% had the short-allele microsatellite polymorphism. There was no significant correlation of either polymorphism with disease severity or with measures of NO production and NOS2 expression. Black and white Americans differed significantly in the frequencies of these polymorphisms. The various association of these gene polymorphisms with malaria severity in different populations underscores the complexity of host resistance to malaria.

Alleles↗

PubMed2004

Elevated nitric oxide production in children with malarial anemia: hemozoin-induced nitric oxide synthase type 2 transcripts and nitric oxide in blood mononuclear cells.

Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMCs) is significantly elevated in children with MA and inversely associated with hemoglobin levels. Additional experiments using PBMCs from non-malaria-exposed donors demonstrate that physiologic amounts of P. falciparum-derived hemozoin augment NOS type 2 (NOS2) transcripts and NO production. Results of these experiments illustrate that elevated NO production in children with MA is associated with decreased hemoglobin concentrations and that hemozoin can induce NOS2-derived NO formation in cultured blood mononuclear cells.

Anemia↗

PubMed1998

Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat.

OBJECTIVE: Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affect myocardial oxygen consumption. Although NOS3 is a constitutive protein, its levels of expression can be modified by various physiological and pathophysiological stimuli. We investigated whether the cell-specific expression of NOS3 mRNA and protein are altered in cardiac hypertrophy. METHODS: Left ventricular cardiac myocytes and coronary microvascular endothelial cells were freshly isolated from 12 week old male spontaneously hypertensive rat (SHR) and matched normotensive Wistar rat hearts. NOS3 protein levels were assessed by Western analysis, and mRNA levels by RT-PCR and Southern blotting. RESULTS: Left ventricular/body weight ratios were significantly increased in SHR compared to Wistar controls, indicating significant hypertrophy. The levels of NOS3 protein were markedly decreased in SHR compared to Wistar cardiac myocytes (by approximately 85%). By contrast, the expression of NOS3 mRNA normalized for GAPDH was increased approximately 3 fold in SHR cardiac myocytes relative to Wistar controls. In freshly isolated microvascular endothelial cells, however, levels of NOS3 protein and NOS3 mRNA were similar between the two groups. CONCLUSIONS: The expression of NOS3 is selectively altered in cardiac myocytes but not coronary microvascular endothelial cells of young SHR hearts, with a marked decrease in NOS3 protein but an increase in NOS3 mRNA. This dysregulation of NOS3 could contribute to contractile dysfunction in left ventricular hypertrophy.

Animals↗

PubMed1995

Role of Sp1 in transcriptional activation of human nitric oxide synthase type III gene.

Endothelial nitric oxide synthase (eNOS or NOS-III) is constitutively expressed. To elucidate the mechanism by which the basal expression of NOS-III gene is activated, we constructed in a luciferase vector, pXP1, serial 5'-deletion mutants of a 1.3-kb 5'-flanking fragment and transiently expressed them in cultured human endothelial cells. The promotor activity was detected in the -198/+22 region which contains several putative Sp1 binding sites. DNase I footprinting assays coupled with gel shift assays revealed the GC box(-104/-90) to be the Sp1 binding site. Site-directed mutation of 4 crucial bases in this site reduced the promotor activity by > 90%. These findings provide strong evidence that binding of Sp1 or closely related protein to this site is required for the activation of basal NOS-III transcription.

Amino Acid Oxidoreductases↗

PubMed2003

Localization of nitric oxide synthase type III in the internal thoracic and radial arteries and the great saphenous vein: a comparative immunohistochemical study.

BACKGROUND: Endothelial nitric oxide synthase type III is the key enzyme of the nitric oxide production in the vessel wall. In this study the localization of endothelial nitric oxide synthase type III within the wall of the human internal thoracic and radial arteries and the great saphenous vein was investigated. METHODS: Specimens were harvested from 23 patients undergoing surgical myocardial revascularization and submitted to light and electron microscope analysis using histochemical stainings and immunohistochemistry with specific antibodies anti-endothelial nitric oxide synthase type III, Factor VIII, and alpha-smooth muscle actin. RESULTS: Endothelial nitric oxide synthase type III was evident in the intima of all conduits and, unexpectedly, in the muscle cells of the media of muscular internal thoracic arteries and radial arteries. No endothelial nitric oxide synthase type III expression was found in the media of great saphenous veins. Semiquantitative analysis revealed a higher endothelial nitric oxide synthase type III expression in the wall of internal thoracic artery, particularly at the level of the media. CONCLUSION: Endothelial nitric oxide synthase type III is expressed in the intima of the internal thoracic and radial artery and the great saphenous vein and in the muscle cells of the media of the internal thoracic and radial arteries. However, the internal thoracic artery shows a higher intensity of endothelial nitric oxide synthase type III expression, particularly within the media. The present study provides the first demonstration of the endothelial nitric oxide synthase type III expression at the level of the smooth muscle cells of the tunica media of systemic human arteries and can provide an histologic explanation for the better results of the internal thoracic artery when used for coronary artery bypass grafting.

Actins↗

PubMed2002

Distinct dimer interaction and regulation in nitric-oxide synthase types I, II, and III.

Homodimer formation activates all nitric-oxide synthases (NOSs). It involves the interaction between two oxygenase domains (NOSoxy) that each bind heme and (6R)-tetrahydrobiopterin (H4B) and catalyze NO synthesis from L-Arg. Here we compared three NOSoxy isozymes regarding dimer strength, interface composition, and the ability of L-Arg and H4B to stabilize the dimer, promote its formation, and protect it from proteolysis. Urea dissociation studies indicated that the relative dimer strengths were NOSIIIoxy >> NOSIoxy > NOSIIoxy (endothelial NOSoxy (eNOSoxy) >> neuronal NOSOXY (nNOSoxy) > inducible NOSoxy (iNOSoxy)). Dimer strengths of the full-length NOSs had the same rank order as judged by their urea-induced loss of NO synthesis activity. NOSoxy dimers containing L-Arg plus H4B exhibited the greatest resistance to urea-induced dissociation followed by those containing either molecule and then by those containing neither. Analysis of crystallographic structures of eNOSoxy and iNOSoxy dimers showed more intersubunit contacts and buried surface area in the dimer interface of eNOSoxy than iNOSoxy, thus revealing a potential basis for their different stabilities. L-Arg plus H4B promoted dimerization of urea-generated iNOSoxy and nNOSoxy monomers, which otherwise was minimal in their absence, and also protected both dimers against trypsin proteolysis. In these respects, L-Arg alone was more effective than H4B alone for nNOSoxy, whereas for iNOSoxy the converse was true. The eNOSoxy dimer was insensitive to proteolysis under all conditions. Our results indicate that the three NOS isozymes, despite their general structural similarity, differ markedly in their strengths, interfaces, and in how L-Arg and H4B influence their formation and stability. These distinguishing features may provide a basis for selective control and likely help to regulate each NOS in its particular biologic milieu.

Amino Acid Sequence↗

PubMed1996

In situ identification of messenger RNA of endothelial type nitric oxide synthase in rat cardiac myocytes.

The endothelial type nitric oxide synthase (NOS) termed as NOS-III has been demonstrated in various nonendothelial cells. Although NOS-III was recently found in the cardiac tissues, identification of the cells expressing NOS-III gene in the heart remains unknown. In this study, we compared the expression of NOS-III mRNA in various tissues of rats by Northern blot analysis using a homologous cDNA probe and identified the cell type by in situ hybridization histochemistry with a cRNA probe. NOS-III mRNA was found more abundantly in atria and ventricle than in other various tissues examined. NOS-III mRNA was intensely and specifically visualized in the cardiac myocytes as well as in the endothelial cells of the heart. No staining was seen with a sense cRNA probe. These results provide the first in vivo evidence for NOS-III mRNA in the cardiac myocytes and suggest its role in the regulation of cardiac functions.

Animals↗

PubMed1998

Inhibitory effect of inducible type nitric oxide synthase on oxidative modification of low density lipoprotein by vascular smooth muscle cells.

Oxidative modification of low density lipoprotein (LDL) plays an important role in atherogenesis. Inducible type nitric oxide synthase (iNOS) has been shown to be expressed in vascular smooth muscle cells (VSMC) of atherosclerotic arteries. Nitric oxide (NO) donors have been shown to inhibit metal ion- or cell-mediated oxidation of LDL. To elucidate whether NO produced by iNOS in VSMC inhibit oxidation of LDL, we investigated the effect of NO donors and iNOS-induction in VSMC on oxidation of LDL. NO donor, S-Nitroso-n-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1) (0.1-1.0 mmol/l) dose-dependently reduced copper-induced oxidation of LDL as demonstrated by the inhibition of electrophoretic mobilities on agarose gels and the formation of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes. Moreover, treatment with IL-1beta (5-50 ng/ml) reduced the increases in electrophoretic mobilities on agarose gels and TBARS formation in association with increases in NO production. In addition, inhibition of NO production by NG-monomethyl-L-arginine monoacetate reduced the inhibitory effect of IL-1beta on LDL oxidation. These results indicate that NO release via iNOS action induced by cytokines in VSMC may play protective roles in oxidative modification of LDL during the atherosclerosis process.

Animals↗

PubMed1996

Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression.

Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.

Blotting, Western↗

PubMed1997

Decreased activity of inducible nitric oxide synthase type 2 and modulation of the expression of glutathione S-transferase alpha, bcl-2, and metallothioneins during the differentiation of CaCo-2 cells.

Reactive oxygen species modulate the cell growth of a wide variety of mammalian cells. To determine whether oxidative metabolism is altered during the differentiation process, we studied the expression of pro- and antioxidant proteins in proliferating and differentiated CaCo-2 cells, a human colon adenocarcinoma cell line. Nitric oxide synthase type 2 (iNOS) produces nitric oxide (NO). Depending on its rate of synthesis, NO may either promote cellular and DNA damage or reduce the ability of other free radicals to induce cell injury. Using Western and Northern blot analysis and arginine conversion assay, we demonstrate that the expression of iNOS decreases when cells undergo differentiation. This biological event entails a diminished production of NO metabolites and correlates with the loss of activation of soluble guanylate cyclase activity. In differentiated cells, a 2-fold down-regulation of the nuclear factor kappa B activity was observed, suggesting that nuclear factor kappa B could be one of the iNOS gene regulatory factors in the CaCo-2 model. In parallel, we studied the expression of other antioxidant proteins including glutathione S-transferase alpha (GST alpha), bcl-2, and the metallothioneins (MTs). We show that the protein levels of GST alpha and MT increase during the differentiation of CaCo-2 cells, whereas bcl-2 levels decrease. Our investigation indicates that the expression of iNOS, GST alpha, bcl-2, and MT is associated with the enterocytic differentiation. The shift in the expression of specific antioxidant genes during CaCo-2 cell differentiation may occur to avoid alterations in the cell redox potential.

Actins↗

PubMed1997

Immunohistochemical localization of nitric oxide synthase in normal human skin: expression of endothelial-type and inducible-type nitric oxide synthase in keratinocytes.

Nitric oxide (NO) is a critical mediator of various biological functions. NO is generated from L-arginine by nitric oxide synthase (NOS), which has three isoforms; endothelial-type NOS (eNOS) and brain-type NOS (bNOS) are constitutive enzymes, and inducible-type NOS (iNOS) is expressed after stimulation. We investigated the expression of NOS in normal human skin by an immunohistochemical technique and western blotting analysis. In human skin, epidermal keratinocytes and the outer root sheath were labeled with not only eNOS antibody but also with iNOS antibody. Both eNOS and iNOS protein in epidermal keratinocytes were confirmed by western blotting. eNOS immunoreactivity was observed in endothelial cells, fibroblasts, the arrector pili muscle, apocrine secretory gland, eccrine coiled duct, and eccrine secretory gland. bNOS immunoreactivity was observed in mast cells. No staining with anti-bNOS antibody was observed in any other cell type. Our present findings suggest that epidermal keratinocytes in normal human skin contain both eNOS and iNOS.

Apocrine Glands↗

PubMed1999

Direct effect of temperature on the catalytic activity of nitric oxide synthases types I, II, and III.

The effect of temperature (between 5.0 and 45.0 degrees C) on the catalytic activity of nitric oxide synthases types I, II, and III (NOS-I, NOS-II, and NOS-III, respectively) has been investigated, at pH 7.5. The value of V(max) for NOS-I activity increases from 1.8 x 10(1) pmol min(-1) mg(-1), at 5.0 degrees C, to 1.8 x 10(2) pmol min(-1) mg(-1), at 45.0 degrees C; on the other hand, the value of K(m) (=4.0 x 10(-6) M) is temperature independent. Again, the value of V(max) for NOS-II activity increases from 8.0 pmol min(-1) mg(-1), at 7.0 degrees C, to 5.4 x 10(1) pmol min(-1) mg(-1), at 40.0 degrees C, the value of K(m) (=1.8 x 10(-5) M) being unaffected by temperature. Temperature exerts the same effect on NOS-I and NOS-II activity, as shown by the same values of DeltaH(V(max)) (=4.2 x 10(1) kJ mol(-1)), DeltaH(K(m)) (=0 kJ mol(-1)), and DeltaH((V(max))(/K(m))()) (=4.2 x 10(1) kJ mol(-1)). On the contrary, the value of K(m) for NOS-III activity decreases from 3.8 x 10(-5) M, at 10.0 degrees C, to 1.6 x 10(-5) M, at 40.0 degrees C, the value of V(max) (=6.8 x 10(1) pmol min(-1) mg(-1)) being temperature independent. Present results indicate that temperature influences directly NOS-I and NOS-II activity independently of the substrate concentration, the values of K(m) being temperature independent. However, when l-arginine level is higher than 2 x 10(-4) M, as observed under in vivo conditions, NOS-III activity is essentially unaffected by temperature, the substrate concentration exceeding the value of K(m). As a whole, although further studies in vivo are needed, these observations seem to have potential physiopathologic implications.

Animals↗

PubMed2000

Protective effect of inducible type nitric oxide synthase against intracellular oxidative stress caused by advanced glycation end-products in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats.

OBJECTIVE: A recent study demonstrated that free radicals were involved in the maintenance of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). However, the role of oxidative stress in hypertension and its related diseases in SHRSP remains unknown. On the other hand, advanced glycation end-products (AGEs) accumulate progressively in the vasculature with ageing, and have been identified to be as relevant mediators for various vascular complications. To elucidate whether nitric oxide (NO) produced by inducible type NO synthase (iNOS) in vascular smooth muscle cells (VSMC) taken from SHRSP and Wistar-Kyoto rats (WKY) attenuate AGEs-induced oxidative stress, we investigated the effect of NO donors and iNOS-induction in VSMC on intracellular oxidant level caused by AGEs. METHODS: The cells preincubated with or without NO donor, S-nitroso-n-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1), IL-1beta and/or N(G)-monomethyl-L-arginine monoacetate (L-NMMA), were treated with AGEs, and the intracellular oxidant levels, total glutathione (GSH) levels, and gamma-glutamylcysteine synthetase (GCS) mRNA were determined. We also determined the expression of an iNOS in VSMC from SHRSP and WKY. RESULTS: The intracellular oxidant level of VSMC was induced by AGEs in a dose-dependent manner. NO donor dose-dependently reduced AGEs-stimulated intracellular oxidant level. Treatment with IL-1beta reduced the AGEs-stimulated intracellular oxidant level through increased NO production, whilst inhibition of NO production by L-NMMA reduced the inhibitory effect of IL-1beta. We also confirmed that NO production as well as the expression of iNOS mRNA and the protein itself were significantly decreased in response to IL-1beta in VSMC from SHRSP compared with WKY. We also confirmed that total GSH levels, decreased by AGEs, were restored by stimulation with IL-1beta. Increased GSH synthesis was due to enhanced expression of the rate-limiting enzyme for GSH synthesis, GCS. These results indicate that NO release, produced by iNOS in VSMC in response to cytokines, might play a protective role against AGEs-stimulated oxidative stress in VSMC. This protective effect of NO is decreased in SHRSP compared to WKY.

Albumins↗

PubMed1996

Expression of nitric oxide synthase type II in the spinal cord under conditions producing thermal hyperalgesia.

There is evidence supporting spinal cord nitric oxide (NO) production in the mechanisms underlying hyperalgesia, presumed to arise from the activity of neuronal nitric oxide synthase type I (NOS I). Intrathecal administration of interleukin-1 beta and interferon-gamma to rats results in a thermal hyperalgesia which peaks at 2 h post-injection but which is undetectable 8 h post-injection. Expression of mRNA for nitric oxide synthase type II (NOS II) was detected by reverse transcription-polymerase chain reaction followed by Southern hybridization utilizing specific oligonucleotides in spinal cord tissue from animals 4 h and 8 h after cytokine injection, but not at longer time points. NOS II protein was detected in soluble fractions of spinal cords from animals 4 h and 8 h after cytokine injection. In situ hybridization for NOS II mRNA revealed positive cells bilaterally in the spinal cord 4 h after cytokine injection in a perivascular distribution and scattered throughout the gray and white matter. Immunohistochemistry for NOS II showed a similar distribution which could only be partially accounted for by macrophages/microglia. These results provide evidence for induction of NOS II expression under conditions producing thermal hyperalgesia and suggest a possible role in this behavior for the production of NO by a variety of cell types in the CNS.

Animals↗

PubMed1998

Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice.

Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a-/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/- 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a-/- mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a-/- mice.

Angiotensin I↗

PubMed2007

Effects of a nitric oxide synthase Type II inhibitor on compound action potential thresholds in experimental endolymphatic hydrops.

HYPOTHESIS: Nitric oxide (NO) is likely to be synthesized by nitric oxide synthase Type II (NOS II) action and may partake in the origin of changes of compound action potential (CAP) threshold observed in guinea pigs with induced endolymphatic hydrops. This study aimed to assess the action of a NOS II inhibitor on CAP thresholds in these experimental samples. BACKGROUND: In guinea pigs with experimental endolymphatic hydrops, there are lesions on the cochlea and progressive increase of CAP threshold. NOS II was found in the cochlea of this animal model, and it was inferred that NO can contribute by such alterations. METHODS: The animals were divided into two groups, in which eight received an intake of a NOS II inhibitor, aminoguanidine, and another eight served as a control group. During 16 weeks, CAP thresholds at 1,000, 2,000, 4,000 and 6,000 on electrocochleography were compared between the groups. RESULTS: The group that had an intake of aminoguanidine showed a lower increase on CAP thresholds at 2,000 (p < 0.05) and 6,000 Hz (p < 0.05) at the 12th postoperative week, and at 1,000 (p < 0.05), 2,000 (p < 0.001), 4,000 (p < 0.001), > and 6,000 Hz (p < 0.001) at the 16th week. CONCLUSION: We conclude that NOS II inhibitor reduced the elevation of CAP thresholds in experimentally induced endolymphatic hydrops.

Action Potentials↗