Neurotransmitter-Loaded Nanocapsule Triggers On-Demand Muscle Relaxation in Living Organism.

This paper reports the on-demand artificial muscle relaxation using a thermosensitive liposome encapsulating γ-aminobutyric acid (GABA) inhibitory neurotransmitter. Muscle relaxation is not feasible in principle, although muscle contraction can be easily induced by electrical stimulation. Herein, thermosensitive liposomes (phase transition temperature = 40 °C) were synthesized to encapsulate GABA and were injected into a leg of a living beetle. The leg was wrapped around by a Ni-Cr wire heater integrated with a thermocouple to enable the feedback control and to manipulate the leg temperature. The injected leg was temporarily immobilized by heating it up to 45 °C. The leg did not swing even by electrically stimulating the leg muscle. Subsequently, the leg recovered to swing. The result indicates that GABA was released from liposomes and fed to the leg muscle, enabling temporal muscle relaxation.

Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser.

PURPOSE: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser. MATERIALS AND METHODS: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10(-5) M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470-500 nm) with and without NOBL-1 (10(-6) M). In addition, we noted rats' responses to light with vardenafil (10(-6) M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10(-5) M), were measured. All measurements were performed in pretreated L-NAME (10(-4) M) conditions to inhibit endogenous NO production. RESULTS: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. CONCLUSIONS: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

Quantitative assessment of the masseter muscle's elasticity using Acoustic Radiation Force Impulse.

AIMS: The study proposes Acoustic Radiation Force Impulse (ARFI) assessment of the masseter muscle elasticity in the healthy population and in patients who have undergone head and neck radiation therapy. PATIENTS AND METHODS: Twenty-five healthy controls constituted group A, and 13 patients who had underwent radiotherapy (35Gy minimum) formed group B. ARFI was performed bilaterally in the periphery (P) and the muscle center (C), in relaxation and contraction. Means and standard deviations were obtained for the recorded shear waves velocities (SWV). RESULTS: For group A: in the relaxed right muscle C = 1.87±0.52 m/s and P = 1.96 ±0.55 m/s and in the left muscle C = 1.66 +/- 0.47 m/s, P = 1.67 +/-0.53 m/s. For group B, in relaxation, the right side presented C = 1.67 +/-0.6 m/s, P 1.72 +/-0.56 m/s, the left muscle C = 1.6 +/-0.34 m/s, P = 1.73 +/-0.37 m/s. There were no differences (p> 0.05) between P and C of both groups, regardless of the muscle state. The values for relaxation and contraction in A and B (merged values of the right and left) presented no differences (1.79+/-0.52 m/s vs 1.72 +/-0.73 m/s, p = 0.72 and 1.70 +/-0.48 m/s and vs 1.59 +/-0.77 m/s, p = 0.98). All measurements of group A vs B were not different (1.79 +/-0.52 m/s vs 1.65 +/-0.63 m/s, p = 0.78). CONCLUSIONS: ARFI with SWV measurement enables the quantification of normal and post irradiation elasticity of the masseter. Further studies on a larger population are required to validate the normal and pathologic values.

Caenorhabditis elegans body mechanics are regulated by body wall muscle tone.

Body mechanics in the nematode Caenorhabditis elegans are central to both mechanosensation and locomotion. Previous work revealed that the mechanics of the outer shell, rather than internal hydrostatic pressure, dominates stiffness. This shell is comprised of the cuticle and the body wall muscles, either of which could contribute to the body mechanics. Here, we tested the hypothesis that the muscles are an important contributor by modulating muscle tone using optogenetic and pharmacological tools, and measuring animal stiffness using piezoresistive microcantilevers. As a proxy for muscle tone, we measured changes in animal length under the same treatments. We found that treatments that induce muscle contraction generally resulted in body shortening and stiffening. Conversely, methods to relax the muscles more modestly increased length and decreased stiffness. The results support the idea that body wall muscle activation contributes significantly to and can modulate C. elegans body mechanics. Modulation of body stiffness would enable nematodes to tune locomotion or swimming gaits and may have implications in touch sensation.

Radiofrequency (GFX) ablation for the reduction of glabellar frowning.

A new minimally invasive procedure is described for the reduction of glabellar frowning. Glabellar furrow relaxation or GFX (TM) utilizes bipolar radiofrequency energy targeted at peripheral motor nerve fibers to the depressor muscles of the forehead. This procedure is a useful adjunct in forehead rejuvenation when performed concomitantly with blepharoplasty or forehead lifting in a surgical setting. With proper training the procedure can be performed under local anesthesia in the office setting to produce very natural results. The relevant anatomy and technique is described here in detail because this represents new knowledge in facial plastic surgery. A cohort of patients has been studied for over 12 months demonstrating the efficacy of the relaxation that can be achieved with the procedure. The GFX procedure offers the patients and surgeons an alternative treatment to botulinum toxin A when longer lasting relaxation of the forehead depressor muscles is desired.

Involvement of contractile elements in control of bioluminescence in Northern krill, Meganyctiphanes norvegica (M. Sars).

Inside the light organs of the bioluminescent (light-producing) crustacean Meganyctiphanes norvegica (krill), numerous capillaries drain haemolymph into the light-producing structure (lantern). We have investigated the arrangement and function of filamentous material found around the opening of the capillaries. These have been suggested to work as sphincters, controlling the haemolymph (i.e. oxygen) supply to the lantern and thereby the production of light. Electron microscopy shows that the filamentous material consists of thick and thin muscle filaments arranged in perpendicular blocks around the opening of each capillary. The actin probe rhodamine phalloidin has revealed that one component is filamentous actin. Clusters of vesicle-dense nerve profiles surround the cells containing filamentous material and antibodies against 5-hydroxytryptamine (5-HT) reveal that 5-HT containing nerves lead to the filamentous area. When exposed to the muscle-relaxing substances papaverine and verapamil, krill respond with luminescence, suggesting that the sphincter structures are functionally involved in the control of light production. Treatment with the muscle-contracting drugs Bay K8544 and thapsigargin gives no light response. Thus, 5-HT stimulates light production in krill; however, a combination of 5-HT and the muscle-relaxing drugs or Bay K8544 potentiates the effect of 5-HT. Thapsigargin quenches the response to 5-HT. Our results corroborate speculations of earlier authors who have suggested that the sphincter structures are of a muscular nature and important in controlling light production in krill. However, other parameters in addition to the oxygen supply to the lantern are involved in controlling bioluminescence in the light organs of M. norvegica.

Low level lasers in dentistry.

Low level laser therapy (LLLT) uses light energy, in the form of adenosine triphosphate (ATP), to elicit biological responses in the body. The increased cellular energy and changes in the cell membrane permeability result in pain relief, wound healing, muscle relaxation, immune system modulation, and nerve regeneration. This article investigates the clinical effects of LLLT and explains how it can be applied in the dental field.

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation.

Using a nitric oxide (NO)-specific fluorescent probe, we have examined the location of NO generation in the urethra from sheep and rat when induced by either electrical field- or light-stimulation (EFS and LS, respectively). In addition, we studied the effect of specific glutathione (GSH) modifiers, acting upon different cellular GSH pools, on NO release and on urethral relaxation. Both EFS and LS led to fluorescence emission from a fiber network associated with neuronal NO synthase (nNOS) immunoreactive nerves. Both the relaxation and the fluorescence elicited by EFS were blocked by specific nNOS inhibitors, but these parameters were not significantly modified by endogenous GSH depletion. In contrast, the opposite was found for LS-induced responses. Moreover, when the mitochondrial pool was effectively reduced by incubation with ethacrynic acid, the responses to LS were further reduced until they disappeared after intensive LS. Our results confirm that while NO is released by nNOS activation, the photolytic breakdown of an endogenous nitro-compound, probably S-nitroso-glutathione, in nitrergic nerves (and in the vascular endothelium) is the only factor responsible for photo-relaxation. The possible role of this mechanism in NO inactivation and as a protective mechanism in NO-generating structures is further discussed.

Differential inhibitory control of circular and longitudinal smooth muscle layers of Balb/C mouse small intestine.

We examined the inhibitory mediators acting on each of the longitudinal (LM) and circular muscle (CM) layers of mouse small intestine in the presence of atropine, prazosin and timolol. Nitric oxide (NO) and apamin-sensitive mediators exerted an inhibitory tone on pacing frequency in CM, observed as an increased frequency upon treatment with N-omega-nitro-l-arginine (LNNA) or apamin. This effect was not seen in LM. 1H-(1,2,4)oxadiazolo(4,3-A)quinazoline-1-one (ODQ) abolished the relaxation in response to electric field stimulation (EFS) in LM in a manner similar to LNNA indicating that the inhibitory mediator in this layer in NO acting via soluble guanylate cyclase. On the other hand, in CM neither LNNA nor apamin was capable of reducing the inhibition in response to EFS and their combination left a residual relaxation of 25%. ODQ reduced the EFS-evoked relaxation more effectively than LNNA at higher frequencies indicating that another ODQ-sensitive mediator was active in CM. ODQ also blocked the relaxation to exogenous vasoactive intestinal peptide in CM. In LM, the relaxation due to sodium nitroprusside was equally blocked by ODQ and apamin, while in CM, its effects were only reduced by ODQ and not apamin. These results indicate that there are differences in the inhibitory mediators and the mechanisms of action involved in LM and CM relaxation.

The location of photodegradable nitric oxide store in the mouse stomach fundus.

The aim of this study was to investigate the location of photodegradable nitric oxide (NO) store using a pharmacological approach in mouse gastric fundus. The ultraviolet light irradiation (UV; 360 nm, 60 s), electrical field stimulation (EFS; 4 Hz, 25 V, 1 ms, 15s-train), exogenous nitric oxide (NO; 10 microM), nitroglycerin (100 microM) and isoproterenol (5 nM) induced relaxation in mouse gastric fundus preparations in the absence or presence of an intact mucosa. The NO scavenger, haemoglobin (20 microM), significantly inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS and NO, but not to nitroglycerin and isoproterenol. The superoxide anion generator, pyrogallol (50 microM), inhibited relaxation of intact and denuded mucosa stomach fundus induced by UV light irradiation, EFS, NO, but not to nitroglycerin and isoproterenol. The inhibition observed with pyrogallol was prevented by exogenous Cu/Zn superoxide dismutase (SOD; 100 U/ml), a membrane impermeable antioxidant. The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS, NO and nitroglycerin but not those to isoproterenol. Exogenous SOD (100 U/ml) partially prevented the inhibitory effect of DETCA on relaxation to UV light irradiation, EFS, NO but not to nitroglycerin. DETCA-induced inhibition of the nitroglycerin-induced relaxation was partially prevented by the cell-permeable polyethylene-glycol-superoxide dismutase (100 U/ml). These results indicate that photodegradable NO store is, at least in part, unlikely to be within smooth muscle cells, and furthermore, that UV light-induced relaxation is not dependent on gastric mucosal layer.

Low level laser therapy partially restores trachea muscle relaxation response in rats with tumor necrosis factor alpha-mediated smooth airway muscle dysfunction.

BACKGROUND AND OBJECTIVE: It is unknown if the decreased ability to relax airway smooth muscles in asthma and other inflammatory airways disorders can be influenced by low level laser therapy (LLLT) irradiation. To investigate if LLLT could reduce impairment in inflamed trachea smooth muscles (TSM) in rats. STUDY DESIGN/MATERIALS AND METHODS: Controlled rat study where trachea was dissected and mounted in an organ bath apparatus with or without a TNF-alpha solution. RESULTS: Low level laser therapy administered perpendicularly to a point in the middle of the dissected trachea with a wavelength of 655 nm and a dose of 2.6 J/cm(2), partially restored TSM relaxation response to isoproterenol. Tension reduction was 47.0 % (+/-2.85) in the laser-irradiated group compared to 22.0% (+/-2.21) in the control group (P < 0.01). Accumulation of cAMP was almost normalized after LLLT at 22.3 pmol/mg (+/-2.1) compared to 17.6 pmol/mg (+/-2.1) in the non-irradiated control group (P < 0.01). CONCLUSION: Low level laser therapy partially restores the normal relaxation response in inflamed TSM and normalizes accumulation of cAMP in the presence of isoproterenol.

Selective modifiers of glutathione prevent restoration of photorelaxations in mouse gastric fundus.

S-nitrosoglutathione (GSNO) has previously been shown to have a role in ultraviolet (UV) light-elicited relaxations and proposed to account for the photosensitive store in the mouse gastric fundus. Furthermore, the depletion of this photosensitive store and its replenishment via long-term electrical field stimulation were demonstrated in the same tissue. In relation to these results, the aim of the present study was to investigate the putative role of S-nitrosothiols in the restorative effect of long-term electrical field stimulation on the reduced photosensitive store. Two series of UV light-elicited relaxations (photorelaxations) were obtained, and the magnitudes of the responses were 53 +/- 6 and 26 +/- 3%, respectively. The second series of photorelaxations attenuated statistically when compared with those in the first series. Ethacrynic acid (1 microm), diamide (1 microm) and glutathione (1 microm) had no effect on the photorelaxations occurred in the second series of responses. Electrical field stimulation (4 Hz, 25 V, 1 ms, 60 min), applied between two series of photorelaxations, revealed a complete recovery of the attenuated photorelaxations appeared in the second series. N(G)-monomethyl-L-arginine (100 microm), ethacrynic acid (1 microm) and diamide (1 microm) extensively prevented the restorative effect of electrical field stimulation on photorelaxations. In addition, glutathione (1 microm) reversed the prevention achieved by ethacrynic acid and diamide. The conclusion is that the restoration accomplished by electrical field stimulation is because of the activation of nitric oxide synthase, which in turn brings about the regeneration of GSNO proposed to be the photodegradable material store.

The importance of myorelaxants in anesthesia.

Neuromuscular blocking drugs were introduced into clinical practice in 1942. Although these drugs made new surgical techniques possible, they also led to morbidity and mortality owing to respiratory muscle paralysis and paralysis in the face of inadequate anesthesia. Newer competitive antagonists at the neuromuscular junction have been developed that have a more rapid onset of action, including rocuronium and mivacurium, making them suitable for use at the onset of anesthesia. Rapid titratable offset of action has been more difficult to achieve, but has been attempted with the inclusion of ester bonds (mivacurium) and binding agents that are in clinical trials. These novel approaches to pharmaceuticals, along with improved understanding of the physiology of the neuromuscular junction in health and disease, have made surgical treatment possible in a wide breadth of clinical situations.

Neocuproine inhibits the decomposition of endogenous S-nitrosothiol by ultraviolet irradiation in the mouse gastric fundus.

In the present study, we investigated whether copper ions are involved in the decomposition of endogenous S-nitrosothiols by ultraviolet (UV) light irradiation in the mouse gastric fundus. The effects of copper ions and chelators of copper(I) and copper(II), neocuproine and cuprozine, respectively, were studied on relaxations in response to S-nitrosoglutathione, UV irradiation, exogenous nitric oxide (NO), added as acidified NaNO(2), and isoproterenol. UV irradiation of smooth muscle strips induced fast and transient relaxations which were mimicked by exogenous NO. S-Nitrosoglutathione induced concentration-dependent relaxations, which were more sustained than those elicited by UV irradiation or NO. CuCl(2) did not affect relaxations elicited by UV irradiation, exogenous NO and isoproterenol but enhanced those elicited by S-nitrosoglutathione. CuSO(4) but not FeSO(4) mimicked the effect of CuCl(2) on relaxations elicited by S-nitrosoglutathione. Neocuproine, the copper(I)-specific chelator, inhibited both photorelaxation and S-nitrosoglutathione-induced relaxation, and this inhibition was prevented by CuCl(2). In contrast, neocuproine significantly enhanced the relaxations in response to exogenous NO, without affecting the relaxations elicited by isoproterenol. Cuprizone, a specific copper(II) chelator, did not affect relaxations in response to S-nitrosoglutathione, UV irradiation, exogenous NO and isoproterenol. These results suggest that copper(I) and not copper(II) may play a role in the NO release evoked by the light-induced decomposition of endogenous S-nitrosothiols in mouse gastric fundus. Also, results with the selective copper(I) chelator, neocuproine, confirmed our recent findings that the endogenous "store" of S-nitrosoglutathione, rather than NO, acts as an intermediate in photorelaxation of the mouse gastric fundus, and that photorelaxation may be a suitable model to elucidate the nature of endogenous S-nitrosothiols.

Normalization by edaravone, a free radical scavenger, of irradiation-reduced endothelial nitric oxide synthase expression.

We investigated the therapeutic effect of edaravone, a free radical scavenger, on alterations in endothelium-dependent relaxation and endothelial nitric oxide synthase (eNOS) expression in the rabbit ear central artery at 2 weeks after exposure to a dose of 45 Gy radiation with a cobalt60 unit. For treatment with edaravone, edaravone was given daily to the animals from the day before irradiation at an intrapenetreal dose of 10 mg/kg twice a day. The endothelium-dependent relaxant response to acetylcholine was markedly impaired in irradiated vessels. Edaravone treatment improved the response to the level observed in nonirradiated control vessels. Using immunohistochemical and Western blot techniques, we showed that protein expression of eNOS in irradiated vessels was reduced to about 50% of control and that edaravone treatment returned it nearly to intact levels. Gene expression of eNOS, analyzed by reverse transcription-competitive polymerase chain reaction, was found to be reduced from the control level by 47% following irradiation. The reduced level of eNOS mRNA in irradiated vessels was almost completely normalized by edaravone treatment. These results suggest that edaravone has a protective effect on the reduced expression of eNOS and its associated endothelial cell dysfunction in the vessels following irradiation. We thus assume that oxygen-free radicals may be closely related to the irradiation-induced derangement of the eNOS gene regulation.

Nitric oxide and the mechanism of rat vascular smooth muscle photorelaxation.

Photorelaxation of vascular smooth muscle (VSM) was studied using segments of tail artery from normotensive rats (NTR) or spontaneously hypertensive rats (SHR). Isolated vessels with intact endothelium were perfused with Krebs solution containing phenylephrine. Perfusion pressures were recorded while arteries were irradiated with either visible (VIS; lambda=514.5 nm) or long wavelength ultra-violet (UVA; lambda=366 nm) light. VIS light produced a transient vasodilator response: a rapid decrease of pressure that recovered fully during the period (6 min) of illumination. An irradiated artery was refractory to a second period of illumination delivered immediately after the first, but its photosensitivity recovered slowly in the dark, a process called 'repriming'. Photorelaxations generated by UVA light were qualitatively different and consisted of two components: a phasic (or p-) component superimposed on a sustained (or s-) component. The p-component is similar to the VIS light-induced response in that both exhibit refractoriness and repriming depends upon endothelium-derived NO. In contrast, the s-component persists throughout the period of illumination and does not show refractoriness. We conclude that VIS light-induced photorelaxations and the p-component of UVA light-induced responses are mediated by the photochemical release of NO from a finite molecular 'store' that can be reconstituted afterwards in the dark. The s-component of the UVA light-induced response does not depend directly on endothelial NO and may result instead from a stimulatory effect of UVA light on soluble guanylate cyclase. NO-dependent photorelaxation is impaired in vessels from SHR while the s-component is enhanced.

Inhibitory actions of hydroxocobalamin, cyanocobalamin, and folic acid on the ultraviolet light-induced relaxation of the frog upper oesophageal strip.

The applications of ultraviolet (UV) light (336 nm) on the upper oesophageal strips of frog elicited relaxant responses in the presence of NaNO2 (50 microM). The tissues were mounted under the tension 0.5 g in an organ bath containing Ringer solution, maintained at 25 degrees C and gassed with 100% O2. The responses were recorded on a kymograph via an isotonic lever. Antimegaloblastic agents, including hydroxocobalamin (1, 10, and 100 microM), cyanocobalamin (1, 10, 25, and 100 microM), and folic acid (1, 10, 50, 100, and 200 microM), significantly attenuated the relaxation response to UV light. Folinic acid (1, 10, 25, and 100 microM), however, enhanced the relaxation. Pyrogallol (50 microM), hydroquinone (50 microM), and diethyldithiocarbamic acid (8 mM) were found ineffective for attenuation, though FeSO4 (200, 400, and 500 microM) and hemoglobin (50 microM), respectively, exerted significant inhibition. L-arginine methylester (500 microM) did not impair UV-induced relaxation. Based on these results, we concluded that a mechanism involving undefined action(s) of antimegaloblastic drugs may cause alterations in the UV light-induced relaxation of the tissue used.

Spontaneous photo-relaxation of urethral smooth muscle from sheep, pig and rat and its relationship with nitrergic neurotransmission.

1. In the present work we have characterized the relaxant response induced by light stimulation (LS) in the lower urinary tract from sheep, pig and rat, establishing its relationship with nitrergic neurotransmission. 2. Urethral, but not detrusor, preparations showed pronounced photo-relaxation (PR) which declined progressively following repetitive LS. Sheep urethral PR was again restored either spontaneously or (to a greater extent) by exogenous nitric oxide (NO) addition and by electrical field stimulation (EFS) of intrinsic nitrergic nerves. 3. Greater NO generation was detected from sheep urethral than from detrusor homogenates following illumination. 4. Sheep urethral PR was inhibited by oxyhaemoglobin, but not by methaemoglobin, carboxy-PTIO, extracellular superoxide anion generators or superoxide dismutase. Guanylyl cyclase but not adenylyl cyclase activation mediates urethral relaxation to LS. 5. Urethral PR was more resistant to inhibition by L-thiocitrulline than EFS-induced responses, although this agent prevented PR restoration by high-frequency EFS. 6. Urethral PR was TTX insensitive and partially modified in high-K+ solutions. Cold storage for 24 h greatly impaired urethral PR, although it was restored by high-frequency EFS. 7. Repetitive exposure to LS, EFS or exogenous NO induced changes in the shape of the EFS-induced nitrergic relaxation, possibly by pre-synaptic mechanisms. 8. In conclusion, we suggest the presence of an endogenous, photo-labile, nitro-compound store in the urethra, which seems to be replenished by neural nitric oxide synthase activity, indicating a close functional relationship with the nitrergic neurotransmitter.

Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation.

BACKGROUND: Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS: Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS: In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

Glyceryl trinitrate-induced vasodilation is inhibited by ultraviolet irradiation despite enhanced nitric oxide generation: evidence for formation of a nitric oxide conjugate.

Our objective was to determine whether a stabilized form of nitric oxide (NO) such as an S-nitrosothiol, rather than NO itself, is the vasoactive metabolite produced when glyceryl trinitrate (GTN) interacts with vascular smooth muscle. In a control study, NO formation was measured by a chemiluminescence-headspace gas method during the incubation of a prototype S-nitrosothiol, namely, S-nitroso-N-acetylpenicillamine (SNAP), in Krebs' solution. NO formation from SNAP was increased when the incubation was carried out in the presence of UV light, indicating that homolytic photolysis of the S-nitrosothiol had occurred. When GTN was incubated with bovine pulmonary artery (BPA) in the absence of UV light, NO was not measurable until 5 min of incubation. By contrast, in the presence of UV light, NO was measurable as early as 0.5 min, and by 5 min, it was higher than that observed in the absence of UV light. BPA rings were relaxed with SNAP and GTN in the absence of UV light, and EC50 values of 0.24 +/- 0.28 microM and 10 +/- 6 nM, respectively, were observed. In the presence of UV light, the vasodilator response of BPA to SNAP and GTN was attenuated, and EC50 values of 2.7 +/- 3.0 microM and 49 +/- 23 nM, respectively, were observed. Our results are consistent with the idea that GTN biotransformation by vascular smooth muscle results in the production of a stabilized form of NO, possibly an S-nitrosothiol, and that degradation of this metabolite by UV light results in NO formation accompanied by decreased vasodilation.