Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP

2005 ◽  
Vol 288 (3) ◽  
pp. C650-C658 ◽  
Author(s):  
Beatrice A. Williams ◽  
Caiqiong Liu ◽  
Ling DeYoung ◽  
Gerald B. Brock ◽  
Stephen M. Sims
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Cellular Response ◽  
Contractile Response ◽  
Corpus Cavernosum ◽  
Soluble Guanylyl Cyclase ◽  
Adrenergic Stimulation ◽  
No Donor ◽  
No Donors ◽  
Intracellular Ca

Tonic contraction of corpus cavernosum smooth muscle cells (SMCs) maintains the flaccid state of the penis, and relaxation is initiated by nitric oxide (NO), leading to erection. Our aim was to investigate the effect of NO on the smooth muscle cellular response to adrenergic stimulation in corpus cavernosum. Fura-2 fluorescence was used to record intracellular Ca2+ concentration ([Ca2+]i) from freshly isolated SMCs from rat and human. Phenylephrine (PE) transiently elevated [Ca2+]i in the presence and absence of extracellular Ca2+, indicating release from intracellular stores. Whereas the NO donor S-nitroso- N-acetylpenicillamine (SNAP) with sildenafil citrate (SIL) caused no change in basal [Ca2+]i, the PE-induced rise of [Ca2+]i was reversibly inhibited by 27 ± 7% ( n = 21, P < 0.005) in rat and by 55 ± 15% ( n = 9, P < 0.01) in human SMCs. SNAP and SIL also reduced the contractile response to PE. To investigate the mechanism, we applied mediators alone or in combination. The soluble guanylyl cyclase inhibitor ODQ reduced the effect of SNAP and SIL. SIL, cGMP analogs, and NO donors without SIL did not reduce the PE-induced rise of [Ca2+]i. However, the combination of 8-bromo-cGMP with SNAP reduced the Ca2+ peak by 42 ± 9% ( n = 22, P < 0.01). Our results demonstrate that NO and cGMP act synergistically to reduce Ca2+ release from intracellular stores. Reduction of intracellular Ca2+ release may contribute to relaxation of the corpus cavernosum, leading to erection.

Endothelin-1-induced vasoconstriction is inhibited during erection in rats

2001 ◽  
Vol 281 (2) ◽  
pp. R476-R483 ◽  
Author(s):  
T. M. Mills ◽  
D. M. Pollock ◽  
R. W. Lewis ◽  
H. S. Branam ◽  
C. J. Wingard
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Muscle Relaxation ◽  
Corpus Cavernosum ◽  
Smooth Muscle Relaxation ◽  
No Donor ◽  
Intracavernosal Injection ◽  
Endothelin 1

Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before erection sharply reduced the magnitude of subsequent erections. Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with maximal ganglionic stimulation, were 0.62 ± 0.05 before ET-1 injection and 0.31 ± 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was injected during a maximal neurally induced erection, the ability of ET-1 to attenuate subsequent erections was diminished (CCP/MAP 0.75 ± 0.02 before ET-1, 0.61 ± 0.03 after). At submaximal stimulation voltages, injection of ET-1 during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1 was injected during erection induced by intracavernosal injection of the nitric oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed (CCP/MAP 0.53 ± 0.04 before ET-1, 0.45 ± 0.04 after). These findings that ET-1-induced vasoconstriction is attenuated during erection are consistent with the hypothesis that NO mediates erection both by initiating pathways that cause smooth muscle relaxation and by inhibiting the vasoconstrictive actions of ET-1.

Mechanism of cGMP contribution to the vasodilator response to NO in rat middle cerebral arteries

2002 ◽  
Vol 282 (5) ◽  
pp. H1724-H1731 ◽  
Author(s):  
Ming Yu ◽  
Cheng-Wen Sun ◽  
Kristopher G. Maier ◽  
David R. Harder ◽  
Richard J. Roman
Keyword(s):  
Nitric Oxide ◽  
Contractile Response ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
No Donor ◽  
Vasodilator Response ◽  
Vasoconstrictor Response ◽  
High K ◽  
Middle Cerebral Arteries ◽  
Intracellular Ca

This study examined the mechanism by which cGMP contributes to the vasodilator response to nitric oxide (NO) in rat middle cerebral arteries (MCA). Administration of a NO donor, diethylaminodiazen-1-ium-1,2-dioate (DEA-NONOate), or 8-bromo-cGMP (8-BrcGMP) increased the diameter of serotonin-preconstricted MCA by 79 ± 3%. The response to DEA-NONOate, but not 8-BrcGMP, was attenuated by iberiotoxin (10−7 M) or a 80 mM high-K+ media, suggesting that activation of K+channels contributes to the vasodilator response to NO but not 8-BrcGMP. The effects of NO and cGMP on the vasoconstrictor response to Ca2+ were also studied in MCA that were permeabilized with α-toxin and ionomycin. Elevations in bath Ca2+ from 10−8 to 10−5 M decreased the diameter of permeabilized MCA by 76 ± 5%. DEA-NONOate (10−6 M) and 8-BrcGMP (10−4 M) blunted this response by 60%. Inhibition of guanylyl cyclase with 1 H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (10−5 M) blocked the inhibitory effect of the NO donor, but not 8-BrcGMP, on Ca2+-induced vasoconstriction. 8-BrcGMP (10−4 M) had no effect on intracellular Ca2+ concentration ([Ca2+]i) in control, serotonin-stimulated, or α-toxin- and ionomycin-permeabilized vascular smooth muscle cells isolated from the MCA. These results indicate that the vasodilator response to NO in rat MCA is mediated by activation of Ca2+-activated K+ channels via a cGMP-independent pathway and that cGMP also contributes to the vasodilator response to NO by decreasing the contractile response to elevations in [Ca2+]i.

scholarly journals Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide

2017 ◽  
Vol 313 (4) ◽  
pp. G330-G341 ◽  
Author(s):  
Ancy D. Nalli ◽  
Sayak Bhattacharya ◽  
Hongxia Wang ◽  
Derek M. Kendig ◽  
John R. Grider ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Muscle Relaxation ◽  
Colonic Motility ◽  
Soluble Guanylyl Cyclase ◽  
Colonic Transit ◽  
Smooth Muscle Relaxation ◽  
No Donor ◽  
Phosphodiesterase 5

Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cyclic guanosine 5′-monophosphate (cGMP). The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse, and human, l-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser1756 (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor S-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S. The inhibitory effect of l-cysteine, but not NaHS, on PDE5 activity was blocked in cells transfected with CSE siRNA or treated with CSE inhibitor d,l-propargylglycine (dl-PPG), suggesting activation of CSE and generation of H2S in response to l-cysteine. H2S levels were increased in response to l-cysteine, and the effect of l-cysteine was augmented by GSNO in a cGMP-dependent protein kinase-sensitive manner, suggesting augmentation of CSE/H2S by cGMP/PKG pathway. As a result, GSNO-induced relaxation was inhibited by dl-PPG. In flat-sheet preparation of colon, l-cysteine augmented calcitonin gene-related peptide release in response to mucosal stimulation, and in intact segments, l-cysteine increased the velocity of pellet propulsion. These results demonstrate that in colonic smooth muscle, there is a novel interplay between NO and H2S. NO generates H2S via cGMP/PKG pathway, and H2S, in turn, inhibits PDE5 activity and augments NO-induced cGMP levels. In the intact colon, H2S promotes colonic transit. NEW & NOTEWORTHY Hydrogen sulfide (H2S) and nitric oxide (NO) are important regulators of gastrointestinal motility. The studies herein provide the cross talk between NO and H2S signaling to mediate smooth muscle relaxation and colonic transit. H2S inhibits phosphodiesterase 5 activity to augment cGMP levels in response to NO, which, in turn, via cGMP/PKG pathway, generates H2S. These studies suggest that interventions targeted at restoring NO and H2S homeostasis within the smooth muscle may provide novel therapeutic approaches to mitigate motility disorders.

Nitric Oxide Activates Leak K+ Currents in the Presumed Cholinergic Neuron of Basal Forebrain

2007 ◽  
Vol 98 (6) ◽  
pp. 3397-3410 ◽  
Author(s):  
Youngnam Kang ◽  
Yoshie Dempo ◽  
Atsuko Ohashi ◽  
Mitsuru Saito ◽  
Hiroki Toyoda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Basal Forebrain ◽  
Reversal Potential ◽  
Soluble Guanylyl Cyclase ◽  
Outward Current ◽  
Pump Current ◽  
Atp Depletion ◽  
Equilibrium Potential ◽  
No Donor ◽  
Bath Application

Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K+ channels. Many neuromodulators closing leak K+ channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K+ channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso- N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3′,5′-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at –70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K+ equilibrium potential ( EK) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K+ current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 μM Rp-8-bromo-β-phenyl-1,N2-ethenoguanosine 3′,5′-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than EK and close to the reversal potential of Na+-K+ pump current. These observations strongly suggest that NO activates leak K+ channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na+-K+ pump through ATP depletion.

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1261-L1270 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Mark R. Girton ◽  
Matthew J. Metropoulus ◽  
Mandar S. Joshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Age Groups ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Sprague Dawley ◽  
No Donor ◽  
Early Postnatal Development ◽  
Old Rats

Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 μM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 μM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.

Nitric oxide stimulates the stress-activated protein kinase p38 in rat renal mesangial cells

1999 ◽  
Vol 202 (6) ◽  
pp. 655-660
Author(s):  
A. Huwiler ◽  
J. Pfeilschifter
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
Mapk Cascade ◽  
No Donor ◽  
No Donors ◽  
Mitogen Activated Protein ◽  
Rapid Activation

Nitric oxide (NO) has gained increased attention as a diffusible universal messenger that plays a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Recently, we reported that exogenous NO is able to activate the stress-activated protein kinase (SAPK) cascade in mesangial cells. Here, we demonstrate that exposure of glomerular mesangial cells to compounds releasing NO, including spermine-NO and (Z)-1-?N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen?-1-ium+ ++-1,2-diolate (MAHMA-NO), results in an activation of the stress-activated p38-mitogen-activated protein kinase (p38-MAPK) cascade as measured by the phosphorylation of the activator of transcription factor-2 (ATF2) in an immunocomplex kinase assay. Activation of the p38-MAPK cascade by a short stimulation (10 min) with the NO donor MAHMA-NO causes a large increase in ATF2 phosphorylation that is several times greater than that observed after stimulation with interleukin-1beta, a well-known activator of the p38-MAPK pathway. Time course studies reveal that MAHMA-NO causes rapid and maximal activation of p38-MAPK after 10 min of stimulation and that activation declines to basal levels within 60 min. The longer-lived NO donor spermine-NO causes a comparable rapid activation of the p38-MAPK pathway; however, the increased activation state of p38-MAPK was maintained for several hours before control values were reattained after 24 h of stimulation. Furthermore, the NO donors also activated the classical extracellular signal-regulated kinase (ERK) p44-MAPK cascade as shown by phosphorylation of the specific substrate cytosolic phospholipase A2 in an immunocomplex kinase reaction. Both MAHMA-NO and spermine-NO cause a rapid activation of p44-MAPK after 10 min of stimulation. Interestingly, there is a second delayed peak of p44-MAPK activation after 4–24 h of stimulation with NO donors. These results suggest that there is a differential activation pattern for stress-activated and mitogen-activated protein kinases by NO and that the integration of these signals may lead to specific cell responses.

Effects of Hypoxic Acclimation, Muscle Strain and Contraction Frequency on Nitric Oxide-Mediated Myocardial Performance in Steelhead Trout (Oncorhynchus mykiss)

2021 ◽  
Author(s):  
Christian Carnevale ◽  
Douglas A. Syme ◽  
A. Kurt Gamperl
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Soluble Guanylyl Cyclase ◽  
Surprising Result ◽  
Muscle Strain ◽  
No Donor ◽  
Contraction Frequency ◽  
Mediated Effects ◽  
Oxide Synthase ◽  
Hypoxic Acclimation

Whether hypoxic acclimation influences nitric oxide (NO)-mediated control of fish cardiac function is not known. Thus, we measured the function / performance of myocardial strips from normoxia and hypoxia-acclimated (40% air saturation; ~ 8 kPa O2) trout at several frequencies (20 - 80 contractions min-1) and two muscle strain amplitudes (8 and 14%) when exposed to increasing concentrations of the NO donor sodium nitroprusside (SNP) (10-9 to 10-4 M). Further, we examined the influence of: 1) nitric oxide synthase (NOS) produced NO (by blocking NOS with 10-4 M L-NMMA); and 2) soluble guanylyl cyclase mediated, NOS-independent, NO effects (i.e., after blockade with 10-4 M ODQ), on myocardial contractility. Hypoxic acclimation increased twitch duration by 8-10% and decreased mass-specific net power by ~35%. However, hypoxic acclimation only had minor impacts on the effects of SNP and the two blockers on myocardial function. The most surprising result of this study was the degree to which contraction frequency and strain amplitude influenced NO-mediated effects on myocardial power. For example, at 8% strain 10-4 SNP resulted in a decrease in net power of ~30% at 20 min-1 but an increase of ~20% at 80 min-1, and this effect was magnified at 14% strain. This study: suggests that hypoxic acclimation has only minor effects on NO-mediated myocardial contractility in salmonids; is the first to report the highly frequency- and strain-dependent nature of NO effects on myocardial contractility in fishes; and supports previous work showing that NO effects on the heart (myocardium) are finely tuned spatio-temporally.

Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes

2001 ◽  
Vol 91 (5) ◽  
pp. 2117-2124 ◽  
Author(s):  
Leo M. A. Heunks ◽  
Herwin A. Machiels ◽  
P. N. Richard Dekhuijzen ◽  
Y. S. Prakash ◽  
Gary C. Sieck
Keyword(s):  
Nitric Oxide ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Similar Data ◽  
Release Channel ◽  
No Donor ◽  
No Donors ◽  
Subsequent Exposure ◽  
Skeletal Myotubes ◽  
Dose Dependent

In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetylcholine (ACh; 10 μM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12 mouse skeletal myotubes. We hypothesized that NO reduces [Ca2+]i in activated skeletal myotubes through oxidation of thiols associated with the sarcoplasmic reticulum Ca2+-release channel. Exposure to diethylamine NONOate (DEA-NO) reversibly increased resting [Ca2+]i level and resulted in a dose-dependent reduction in the amplitude of ACh-induced [Ca2+]i responses (25 ± 7% reduction with 10 μM DEA-NO and 78 ± 14% reduction with 100 μM DEA-NO). These effects of DEA-NO were partly reversible after subsequent exposure to dithiothreitol (10 mM). Preexposure to DEA-NO (1, 10, and 50 μM) also reduced the amplitude of the caffeine-induced [Ca2+]i response. Similar data were obtained by using the chemically distinct NO donor S-nitroso- N-acetyl-penicillamine (100 μM). These results indicate that NO reduces sarcoplasmic reticulum Ca2+ release in skeletal myotubes, probably by a modification of hyperreactive thiols present on the ryanodine receptor channel.

scholarly journals Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 121
Author(s):  
Swami Prabhuling ◽  
Yasinalli Tamboli ◽  
Prafulla B. Choudhari ◽  
Manish S. Bhatia ◽  
Tapan Kumar Mohanta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Corpus Cavernosum ◽  
Active Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Muscle Relaxant Activity

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly 10d (1.50 ± 0.6) and 10g (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.

scholarly journals Development of Photoinitiated Nitric Oxide Releasing Polymer Films for Controlled Drug Delivery

2009 ◽  
Vol 3 (2) ◽  
Author(s):  
D. M. Smeenge ◽  
M. J. Barron ◽  
M. T. Nielsen ◽  
J. Goldman ◽  
M. C. Frost
Keyword(s):  
Nitric Oxide ◽  
Drug Delivery ◽  
Smooth Muscle ◽  
Cell Cultures ◽  
Polymer Films ◽  
Surface Flux ◽  
Surface Fluxes ◽  
No Donors ◽  
Polymeric Systems ◽  
Smooth Muscle Cell Cultures

Nitric Oxide (NO) is small, free radical gas that has been shown to have a wide variety of physiological functions, including the ability to hinder tumor angiogenesis at high, but non lethal, concentrations [1]. Previous work suggests that if NO could be effectively delivered in vivo to tumors of patients currently undergoing chemotherapy treatments at the appropriate levels, less damaging chemotherapy treatments could be used against cancer [2]. This could increase the overall survivability of cancer patients, especially in those prone to the harmful effects of chemotherapy: children, elderly, and those of weak immune systems. If NO is especially successful at preventing and eliminating tumor growth, angiogenesis, and carcinogenesis the need for stressful chemotherapy treatments could be eliminated altogether. This project is focused on developing novel photosensitive NO donors that can be incorporated into polymeric systems and used in a fiber optic drug delivery system. Development of these NO-releasing polymers will allow continued investigation of NO's role in tumor death by precisely controlling the surface flux of NO that cells are exposed to. Generating specific surface fluxes of NO from polymer films has been demonstrated by using polymer films that contain photoinitiated NO donors [3], prepared by synthesizing S-nitrosothiol (RSNO) derivitized polymer fillers that are blended into hydrophobic polymers and cast into a film. These films generate and sustain a surface flux of NO based on the wavelength and intensity of light used [3]. Polymers releasing NO are more promising as an NO donor than simply injecting NO into samples because they allow for spatial and temporal control of NO delivery. The specific concentration of NO needed to produce desirable effects on tumor cells (i.e., apoptosis) is not known. Data will be presented that show the synthesis and NO-release properties of novel RSNOs based on the nitrosation of benzyl mercaptan thiols. Specifically, UV-Vis spectrum of benzyl mercaptan in toluene and S-nitrosobenzyl mercaptan after the addition of t-butyl nitrite will be presented. We are currently investigating the effects of varying NO-surface fluxes generated from photolytic NO donating polymer films on aortic smooth muscle cell cultures obtained from mice. Once we have established that we can quantitatively determine the effects of different levels of NO on the proliferation of smooth muscle cell cultures, work will begin to apply this methodology and these novel NO-releasing polymeric systems to begin investigating what durations and surface fluxes of NO are necessary to have tumorcidal effects on specific cancer cells.

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