NO Donor Sodium Nitroprusside (no + donor_sodium_nitroprusside)

Distribution by Scientific Domains

Selected Abstracts

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance

J. A. Simonsen
Abstract Aim:, We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods:, Normal volunteers (23,28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor NG -nitro- l -arginine methyl ester (l -NAME) at 0.5 mg kg,1 h,1. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results:,l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL,1, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL,1, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min,1, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min,1). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions:, Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation. [source]

Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes

Seung-Soo Chung
The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 ,m) completely inhibited Icat oscillations evoked by 1 ,m CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 ,m) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3,,5,-cyclic monophosphate (8-Br-cGMP; 30 ,m) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 ,m) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 ,m) in the pipette solution, CCh (1 ,m) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 ,m) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 ,m) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner. [source]

Nitric oxide reduces astrocytic lactate production and induces neuronal vulnerability in stroke-prone spontaneously hypertensive rats

GLIA, Issue 4 2008
Kazuo Yamagata
Abstract Nitric oxide (NO) leads to neuronal death in ischemia/reperfusion (I/R), including stroke. Here, we examined the NO-induced vulnerability of neurons and lactate production by astrocytes in stroke-prone spontaneously hypertensive rats (SHRSP) in vitro. Neuronal cell death induced by the NO donor sodium nitroprusside (SNP) was significantly increased in SHRSP compared with Wistar kyoto rats (WKY). Furthermore, levels of lactate production by astrocytes were significantly reduced in SHRSP compared with WKY. At the same time, expressions of the lactate dehydrogenase (LDH) and monocarboxylate transporter 1 (MCT1) genes were significantly decreased by SNP in SHRSP compared with WKY. Moreover, in astrocytes isolated from SHRSP, the gene expression of isoforms of 6-phosphofracto-2-kinase (PFK2), a master regulator of glycolysis, namely PFK2.1, PFK2.2, PFK2.3, and PFK2.4, had deteriorated significantly. Notably, the SNP-evoked gene expression of PFK2.4 was lower in astrocytes of SHRSP than those of WKY. These results indicated that the neurons and astrocytes of SHRSP differed in responsiveness to SNP from those of WKY. This difference might explain the deficiency of energy and vulnerability to SNP of the neurons of SHRSP. © 2008 Wiley-Liss, Inc. [source]

Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel

Yaohui Zhu
Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from ,80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at ,25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. [source]

Characterization of Phosphodiesterase Type 5 Expression and Functional Activity in the Human Male Lower Urinary Tract

Benedetta Fibbi MD
ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim., To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures., PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods., In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results., In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions., The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, and Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:59,69. [source]

Erectile Function in Two-Kidney, One-Clip Hypertensive Rats is Maintained by a Potential Increase in Nitric Oxide Production

A. Elizabeth Linder PhD
ABSTRACT Introduction., Hypertension is closely associated with erectile dysfunction (ED) as it has been observed in many experimental models of hypertension. Additionally, epidemiological studies show that approximately a third of hypertensive patients have ED. Aim., To test the hypothesis that the two-kidney, one-clip (2K-1C) rat model of hypertension displays normal erectile function due to increased nitric oxide (NO) production in the penis. Methods., Ganglionic-induced increase in intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was used as an index of erectile function in 2K-1C and in normotensive sham-operated (SHAM) anesthetized rats. Cavernosal strips from hypertensive and normotensive rats were used for isometric tension measurement. The contraction induced by alpha-adrenergic agonist phenylephrine and the relaxation induced by the NO donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the NO synthase inhibitor N, -nitro-L-arginine (L-NNA). Results., Changes in ICP/MAP induced by ganglionic stimulation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were similar in cavernosal strips from both groups. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM. Conclusions., These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is maintained in spite of the increased Rho-kinase activity by increased NO signaling. Linder AE, Dorrance AM, Mills TM, Webb RC, and Leite R. Erectile function in two-kidney, one-clip hypertensive rats is maintained by a potential increase in nitric oxide production. J Sex Med 2009;6(suppl 3):279,285. [source]

Different sensitivity of isoprenaline-induced responses in ventricular muscle to sodium nitroprusside in normotensive and spontaneously hypertensive rats 1

A. M. Manso
1 The aim of the present work was to study the possible modulatory role of nitric oxide (NO) on the positive inotropic effect induced by the ,-adrenoceptor agonist isoprenaline in myocardial contractility, and whether this modulation is altered by hypertension. 2 The study was performed using right ventricular strips from the hearts of 6-month-old male Wistar,Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The contractile force of electrically-stimulated ventricular strips was measured by a force-displacement transducer. 3 Isoprenaline (from 10 nmol l,1 to 10 ,mol l,1) induced a concentration-dependent increase in cardiac contractility in strips from both rat strains. This positive inotropic effect to isoprenaline was reduced by the NO donor sodium nitroprusside (SNP, 0.1 mmol l,1) in muscles from WKY rats and slightly increased in those from SHR. The SNP-induced increase in strips from SHR was abolished by superoxide dismutase (100 U ml,1). 4 NG-nitro-arginine-methyl ester (L-NAME, 0.1 mmol l,1) and 1H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one (ODQ, 10 ,mol l,1), respective inhibitors of NO synthase and guanylate cyclase, increased the response to isoprenaline in muscles from WKY rats, whereas it was unaltered in strips from SHR. 5 In strips from WKY rats, the combination of ODQ and SNP produced an increase in the response elicited by isoprenaline, which was similar to that observed with ODQ or L-NAME. 8-Br-cyclicGMP (8-Br-cGMP, 0.1 mmol l,1), a permeable and structural cGMP analogue, decreased the effect induced by isoprenaline only in muscles from WKY rats. 6 These results suggest that the positive inotropic response to isoprenaline in ventricular strips from WKY rats is negatively modulated by NO, and positively by superoxide anions in those from SHR. The lack of a modulatory response to NO in ventricular strips from SHR is probably a result of an alteration of mechanisms in NO-signalling pathway downstream of cGMP formation in SHR hearts. [source]

Modulation of gap junctions by nitric oxide contributes to the anti-arrhythmic effect of sodium nitroprusside?

Márton Gönczi
Background and purpose:, Nitric oxide (NO) donors provide a preconditioning-like anti-arrhythmic protection in the anaesthetized dog. As NO may modulate gap junction (GJ) function, the present study investigated whether this anti-arrhythmic effect is due to a modification of GJs by NO, derived from the NO donor sodium nitroprusside (SNP). Experimental approach:, In chloralose-urethane-anaesthetized, open-chest dogs, either saline (controls; n= 11) or SNP (0.2 µg·kg,1·min,1; n= 10) was infused at a rate of 0.5 mL·min,1 by the intracoronary route. The infusions were started 20 min prior to and maintained throughout the entire 60 min occlusion period of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, tissue electrical impedance and permeability, as well as the phosphorylation of connexin43, were assessed. Key results:, Compared with the controls, SNP infusion markedly suppressed the total number of ventricular premature beats (666 ± 202 vs. 49 ± 18; P < 0.05), and the number of ventricular tachycardiac episodes (8.1 ± 2.3 vs. 0.2 ± 0.1; P < 0.05) without significantly modifying the incidence of ventricular tachycardia or ventricular fibrillation. The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) and tissue electrical impedance changes were significantly less in the SNP-treated dogs. SNP improved GJ permeability and preserved the phosphorylated form of connexin43. Conclusion and implications:, The anti-arrhythmic protection resulting from SNP infusion in the anaesthethized dog may, in part, be associated with the modulation of gap junctional function by NO. [source]

Effects of nitric oxide and nitrogen on seedling emergence, ion accumulation, and seedling growth under salinity in the euhalophyte Suaeda salsa

Jie Song
Abstract Recently nitric oxide (NO) has emerged as a key signal molecule in plants. However, little is known about the role of NO in the salt tolerance of halophytes. Effects of the NO donors sodium nitroprusside (SNP) and nitrate (NO) on growth and ion accumulation in the euhalophyte Suaeda salsa under salinity were investigated in the present study. The results showed that higher SNP supply increased seedling emergence, but SNP had no effect on shoot growth and the concentrations of Na+, K+, Cl,, and NO. Higher NO had no effect on seedling emergence of the species. Shoot Cl, decreased, but NO3, increased markedly, with a higher NO supply. The decrease in the estimated contribution of Cl, to the osmotic potential was compensated for by an increase in that of NO. It appears that NO plays an important osmotic role in S. salsa under high salinity with a higher NO supply, and this trait may increase salt tolerance of the species under high salinity. [source]

Regulation of nitrate reductase by nitric oxide in Chinese cabbage pakchoi (Brassica chinensis L.)

ABSTRACT Nitrate reductase (NR), a committed enzyme in nitrate assimilation, involves generation of nitric oxide (NO) in plants. Here we show that the NR activity was significantly enhanced by the addition of NO donors sodium nitroprusside (SNP) and NONOate (diethylamine NONOate sodium) to the culturing solution, whereas it was decreased by NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, both NO gas and SNP directly enhanced but cPTIO inhibited the NR activities of crude enzyme extracts and purified NR enzyme. The cPTIO terminated the interaction between NR-generated NO and the NR itself. Furthermore, the NR protein content was not affected by the SNP treatment. The investigation of the partial reactions catalysed by purified NR using various electron donors and acceptors indicated that the haem and molybdenum centres in NR were the two sites activated by NO. The results suggest that the activation of NR activity by NO is regulated at the post-translational level, probably via a direct interaction mechanism. Accordingly, the concentration of nitrate both in leaves and roots was decreased after 2 weeks of cultivation with SNP. The present study identifies a new mechanism of NR regulation and nitrate assimilation, which provides important new insights into the complex regulation of N-metabolism in plants. [source]